Process for the preparation of thietane derivatives

ABSTRACT

The present invention relates to processes for the preparation of thietane derivatives of the formula IA 
     
       
         
         
             
             
         
       
     
     and thietane derivatives of the formula IB 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , B, and n are as defined in the claims. The invention also relates to intermediates useful in the processes, as well as the compounds of formula IA and IB and their use as pesticides.

RELATED APPLICATION INFORMATION

This application is a divisional of U.S. patent application Ser. No.14/240,541 filed 24 Feb. 2014 which was a 371 of InternationalApplication No. PCT/EP2012/066552, filed 24 Aug. 2012, which claimspriority to EP Patent Application No. 11178929.3, filed 25 Aug. 2011,the contents of which are incorporated herein by reference herein.

The present invention relates to processes for the preparation of novelinsecticidally active thietane derivatives. The invention also relatesto the thietane derivatives and to intermediates used in the preparationof the thietane derivatives, as well as methods of using the thietanederivatives to combat and control insect, acarine, nematode and molluscpests.

Certain thietane derivatives with insecticidal properties are disclosed,for example, in WO2009/080250.

New procedures for synthesising insecticidally active thietanederivatives having an alkylene group between the thietane and amidegroups have now surprisingly been discovered, allowing easier andpotentially cheaper access to these compounds, and thereby opening upthe possibility of commercial production.

In a first aspect the invention provides a process for the preparationof a compound of formula IA

whereinA¹, A², A³ and A⁴ are independently of one another C—H, C—R³, ornitrogen;

B is O or CH₂;

R¹ is C₁-C₈haloalkyl;R² is aryl or aryl substituted by one to five R⁴, or heteroaryl orheteroaryl substituted by one to five R⁴;each R³ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkoxycarbonyl-, amino, hydroxy, mercapto, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl, C₁-C₈haloalkylsulfinyl,C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl, C₁-C₈alkylcarbonyl, or twoR³ on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a—N═CH—CH═CH— bridge; each R⁴ is independently halogen, cyano, nitro,C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy,mercapto, C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl,C₁-C₈haloalkylsulfinyl, C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, aryl or aryl substituted by oneto five R⁵, or heterocyclyl or heterocyclyl substituted by one to fiveR⁵;each R⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-;n is 0, 1 or 2;comprising preparing a compound of formula IV

By eithera. reacting a compound of formula II

with a source of cyanide in the presence of water to give a compound offormula III

b. reducing the compound of formula III with a suitable reducing agentto give a compound of formula IV

c-i. reacting the compound of formula IV with a compound of formula V

wherein R is OH, C₁-C₆alkoxy or Cl, F or Br, and R¹, R², B, A¹, A², A³and A⁴ are as defined for compounds of formula IA to give a compound offormula I; orA) reacting a compound of formula VII

with CH₃NO₂ to give a compound of formula XI

B) reducing the compound of formula XI with a suitable reducing agent togive a compound of formula IV; or1) homologating a compound of formula VII

to give an ester of formula XII

wherein R is C₁-C₆alkyl;2) reducing the compound of formula XII using a suitable reducing agentto give a compound of formula XIII

3) treating the compound of formula XIII with hydrazoic acid to give acompound of formula IV;andc-i. reacting the compound of formula IV with a compound of formula V

wherein R is OH, C₁-C₆alkoxy or Cl, F or Br, and R¹, R², B, A¹, A², A³and A⁴ are as defined for compounds of formula I to give a compound offormula IA; orc-ii reacting the compound of formula IV with a compound of formula VI

wherein X^(B) is a leaving group for example a halogen, such as bromo,and R¹, R², B, A¹, A², A³ and A⁴ are as defined for compounds of formulaIAwith carbon monoxide in the presence of a suitable catalyst to give acompound of formula IA;and wherein the method optionally comprises oxidizing the sulfur atom ofthethietane moiety.

The source of cyanide in step a. is for example CN⁻, e.g. provided as acyanide salt such as a alkali metal salt M-CN, wherein M is for examplepotassium or sodium. In step b. a suitable reducing agent is for examplea hydride reagent such as lithium aluminium hydride.

In a further aspect, the invention provides a method of preparing acompound of formula IV

comprisinga. reacting a compound of formula II

with a source of cyanide in the presence of water to give a compound offormula III

b. reducing the compound of formula III with a suitable reducing agentto give a compound of formula IV.

In a further aspect, the invention provides a method of preparing acompound of formula IV

comprisingA) reacting a compound of formula VII

with CH₃NO₂ to give a compound of formula XI

B) reducing the compound of formula XI with a suitable reducing agent togive a compound of formula IV.

In a further aspect, the invention provides a method of preparing acompound of formula IV

comprising1) homologating a compound of formula VII

to give an ester of formula XII

wherein R is C₁-C₆alkyl;2) reducing the compound of formula XII using a suitable reducing agentto give a compound of formula XIII

3) treating the compound of formula XIII with hydrazoic acid to give acompound of formula IV.

In a further aspect the invention provides a compound of formula IA

whereinA¹, A², A³ and A⁴ are independently of one another C—H, C—R³, ornitrogen;

B is O or CH₂;

R¹ is C₁-C₈haloalkyl;R² is aryl or aryl substituted by one to five R⁴, or heteroaryl orheteroaryl substituted by one to five R⁴;each R³ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkoxycarbonyl-, amino, hydroxy, mercapto, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl, C₁-C₈haloalkylsulfinyl,C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl, C₁-C₈alkylcarbonyl, or twoR³ on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a—N═CH—CH═CH— bridge;each R⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl,C₁-C₈haloalkylsulfinyl, C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, aryl or aryl substituted by oneto five R⁵, or heterocyclyl or heterocyclyl substituted by one to fiveR⁵;each R⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-.

In a further aspect the invention provides a process for the preparationof a compound of formula IB,

whereinA¹, A², A³ and A⁴ are independently of one another C—H, C—R³, ornitrogen;

B is O or CH₂;

R¹ is C₁-C₈haloalkyl;R² is aryl or aryl substituted by one to five R⁴, or heteroaryl orheteroaryl substituted by one to five R⁴;each R³ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkoxycarbonyl-, amino, hydroxy, mercapto, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl, C₁-C₈haloalkylsulfinyl,C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl, C₁-C₈alkylcarbonyl, or twoR³ on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a—N═CH—CH═CH— bridge;each R⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl,C₁-C₈haloalkylsulfinyl, C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, aryl or aryl substituted by oneto five R⁵, or heterocyclyl or heterocyclyl substituted by one to fiveR⁵;each R⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-;n is 0, 1 or 2;comprisingi. reacting a compound of formula VII

with triphenylphosphoranyldiene-acetonitrile or(Cyanomethyl)diethoxyphosphine oxide to give a compound of formula VIII

ii. reducing the compound of formula VIII with a suitable reducing agentto give a compound of formula X

iii-i. reacting the compound of formula X with a compound of formula V

wherein R is OH, C₁-C₆alkoxy or Cl, F or Br, and R¹, R², B, A¹, A², A³and A⁴ are as defined for compounds of formula I to give a compound offormula IB; oriii-ii reacting the compound of formula X with a compound of formula VI

wherein X^(B) is a leaving group for example a halogen, such as bromo,and R¹, R², B, A¹, A², A³ and A⁴ are as defined for compounds of formulaIB with carbon monoxide in the presence of a suitable catalyst to give acompound of formula IB; and wherein the method optionally comprisesoxidizing the sulfur atom of the thietane moiety.

In step ii. a suitable reducing agent is for example a hydride reagentsuch as a borohydrate, e.g. sodium borohydride, or lithiumaluminiumhydride. Step ii may be carried out in two steps, e.g. ii-i, reductionto (thietan-3-yl)acetonitrile e.g. with sodium borohydride, and ii-iireduction to (thietan-3-yl)ethanamine with lithiumaluminium hydride.

In steps c-i. and iii-i suitable conditions when R is OH are for examplediisopropylethylamine (Hunig's Base) and a solution ofbis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-CI”), in the presenceof a suitable base.

Suitable conditions when R is halogen are for example the presence of asuitable base. Suitable conditions when R is C₁-C₆alkoxy are for exampleheating. In steps c-ii and iii-ii a suitable catalyst is for example acatalyst comprising palladium such as palladium(II) acetate orbis(triphenylphosphine)palladium(II) dichloride.

In a further aspect the invention provides a process for preparing acompound of formula X

comprisingi. reacting a compound of formula VII

with triphenylphosphoranyldiene-acetonitrile or(Cyanomethyl)diethoxyphosphine oxide to give a compound of formula VIII

ii. reducing the compound of formula VIII with a suitable reducing agentto give a compound of formula X.

In a further aspect the invention provides a compound of formula IB

whereinA¹, A², A³ and A⁴ are independently of one another C—H, C—R³, ornitrogen;

B is O or CH₂;

R¹ is C₁-C₈haloalkyl;R² is aryl or aryl substituted by one to five R⁴, or heteroaryl orheteroaryl substituted by one to five R⁴;each R³ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl,C₂-C₈alkynyl, C₂-C₈haloalkynyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkoxycarbonyl-, amino, hydroxy, mercapto, C₁-C₈alkylthio,C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl, C₁-C₈haloalkylsulfinyl,C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl, C₁-C₈alkylcarbonyl, or twoR³ on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a—N═CH—CH═CH— bridge;each R⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio, C₁-C₈haloalkylthio, C₁-C₈alkylsulfinyl,C₁-C₈haloalkylsulfinyl, C₁-C₈alkylsulfonyl, C₁-C₈haloalkylsulfonyl,C₁-C₈alkylcarbonyl, C₁-C₈alkoxycarbonyl, aryl or aryl substituted by oneto five R⁵, or heterocyclyl or heterocyclyl substituted by one to fiveR⁵;each R⁵ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy-, or C₁-C₄haloalkoxy-;n is 0, 1 or 2.

In a further aspect the invention provides a compound of formula IV orXV

wherein n is 1 or 2.

In a further aspect the invention provides a compound of formula VIII,IX, X or XV

In a further aspect the invention provides a compound of formula XI, XIIor XIII

wherein R is C₁-C₆alkyl.

In a further aspect the invention provides a compound of formula IIIa or

wherein n is 1 or 2.

The above reaction steps are described in more detail below.

The compounds of formula (I) may exist in different geometric or opticalisomers or tautomeric forms. This invention covers all such isomers andtautomers and mixtures thereof in all proportions as well as isotopicforms such as deuterated compounds. The invention also covers salts andN-oxides of all compounds of the invention.

The compounds of the invention may contain one or more asymmetric carbonatoms, for example, in the —CR³R⁴— group or at the LR²Y¹Y⁴ carbon andmay exist as enantiomers (or as pairs of diastereoisomers) or asmixtures of such. Further, where any Y group is SO, the compounds of theinvention are sulfoxides, which can also exist in two enantiomericforms.

Each alkyl moiety either alone or as part of a larger group (such asalkoxy, alkylcarbonyl, or alkoxycarbonyl) is a straight or branchedchain and is, for example, methyl, ethyl, n-propyl, prop-2-yl, n-butyl,but-2-yl, 2-methyl-prop-1-yl or 2-methyl-prop-2-yl. The alkyl groups arepreferably C₁-C₆ alkyl groups, more preferably C₁-C₄ and most preferablyC₁-C₃ alkyl groups.

Alkenyl moieties can be in the form of straight or branched chains, andthe alkenyl moieties, where appropriate, can be of either the (E)- or(Z)-configuration. Examples are vinyl and allyl. The alkenyl groups arepreferably C₂—O₆, more preferably C₂—O₄ and most preferably C₂-C₃alkenyl groups.

Alkynyl moieties can be in the form of straight or branched chains.Examples are ethynyl and propargyl. The alkynyl groups are preferablyC₂—O₆, more preferably C₂—O₄ and most preferably C₂-C₃ alkynyl groups.

Halogen is fluorine, chlorine, bromine or iodine.

Haloalkyl groups (either alone or as part of a larger group, such ashaloalkoxy) are alkyl groups which are substituted by one or more of thesame or different halogen atoms and are, for example, trifluoromethyl,chlorodifluoromethyl, 2,2,2-trifluoro-ethyl or 2,2-difluoro-ethyl.

Haloalkenyl groups are alkenyl groups, respectively, which aresubstituted with one or more of the same or different halogen atoms andare, for example, 2,2-difluorovinyl or 1,2-dichloro-2-fluoro-vinyl.

Haloalkynyl groups are alkynyl groups, respectively, which aresubstituted with one or more of the same or different halogen atoms andare, for example, 1-chloro-prop-2-ynyl.

In the context of the present specification the term “aryl” refers to aring system which may be mono-, bi- or tricyclic. Examples of such ringsinclude phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. Apreferred aryl group is phenyl.

The term “heteroaryl” refers to an aromatic ring system containing atleast one heteroatom and consisting either of a single ring or of two ormore fused rings. Preferably, single rings will contain up to threeheteroatoms and bicyclic systems up to four heteroatoms which willpreferably be chosen from nitrogen, oxygen and sulfur. Examples of (5-6membered) monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl,pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl,furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl,isothiazolyl, and thiadiazolyl. Examples of bicyclic groups includequinolinyl, cinnolinyl, quinoxalinyl, benzimidazolyl, benzothiophenyl,and benzothiadiazolyl. Monocyclic heteroaryl groups are preferred,preferably monocyclic rings containing 1 to 3 heterotoms selected fromO, N or S, e.g. pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl,furanyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, preferablypyridyl, pyrazolyl, furanyl, thiophenyl, thiazolyl, pyridyl being mostpreferred.

The term “heterocyclyl” is defined to include heteroaryl and in additiontheir unsaturated or partially unsaturated analogues.

Preferred values of A¹, A², A³, A⁴, B, R¹, R², R³, R⁴ and R⁵ are, in anycombination, as set out below. These preferred values apply to allcompounds of the invention having any or all of these substituents.

Preferably A¹ is C—H or C—R³ and no more than two of A², A³ and A⁴ arenitrogen, more preferably no more than two of A², A³ and A⁴ are nitrogenand A³ and A⁴ are not both nitrogen. Even more preferably A¹ is C—H orC—R³, A² is C—H, C—R³ or nitrogn, A³ and A⁴ are independently C—H ornitrogen, wherein no more than two of A², A³ and A⁴ are nitrogen, and A³and A⁴ are not both nitrogen, and wherein when A² is C—R³ then the R³ ofA¹ and the R³ of A² together form a —CH═CH—CH═CH— bridge. Yet even morepreferably A¹ is C—R³, A² is C—H, C—R³ or nitrogen, A³ and A⁴ areindependently C—H or nitrogen, wherein no more than two of A², A³ and A⁴are nitrogen, and A³ and A⁴ are not both nitrogen, and wherein when A²is C—R³ then the R³ of A¹ and the R³ of A² together form a —CH═CH—CH═CH—bridge. Yet even more preferably A¹ is C—R³, A² is C—H, and one of A³and A⁴ is C—H and the other is nitrogen.

In one group of compounds A¹ is C—H or C—R³, most preferably A¹ is C—R³.

In one group of compounds A² is C—H or C—R³, most preferably A² is C—H.

In one group of compounds A³ is C—H or C—R³, most preferably A³ is C—H.

In one group of compounds A⁴ is C—H or C—R³, most preferably A⁴ is C—H.

Preferably R¹ is chlorodifluoromethyl, difluoromethyl ortrifluoromethyl, more preferably chlorodifluoromethyl ortrifluoromethyl, most preferably trifluoromethyl.

Preferably R² is aryl or aryl substituted by one to three R⁴, morepreferably R² is phenyl or phenyl substituted by one to three R⁴,pyridyl or pyridyl substituted by one to three R⁴, more preferably R² isphenyl substituted by one to three R⁴ or pyridyl substituted by one tothree R⁴, more preferably R² is group P

wherein X is N or C—R⁴, preferably X is C—R⁴.

More preferably R² is 3,5-bis-(trifluoromethyl)-phenyl,3-chloro-5-trifluoromethyl-phenyl, 3-bromo-5-trifluoromethyl-phenyl,3,5-dibromo-phenyl, 3,5-dichloro-phenyl, 3,4-dichloro-phenyl,3-trifluoromethyl-phenyl, 4-bromo-3,5-dichlorophenyl,3-bromo-5-chlorophenyl, 4-fluoro-3,5-dichlorophenyl or3,4,5-trichloro-phenyl, 3-chloro-4-fluorophenyl,3-fluoro-4-chlorophenyl, 4-bromo-3,5-dichlorophenyl,4-iodo-3,5-dichlorophenyl, 3,4,5-trifluorophenyl,3-chloro-5-fluorophenyl, 3,4-dichloro-5-trifluoromethylphenyl or4-chloro-3,5-bis-(trifluoromethyl)-phenyl, more preferably3,5-bis-(trifluoromethyl)-phenyl, 3-chloro-5-trifluoromethyl-phenyl,3,5-dichloro-phenyl, 3-trifluoromethyl-phenyl,4-bromo-3,5-dichlorophenyl, 3-bromo-5-chlorophenyl,4-fluoro-3,5-dichlorophenyl, 3,4,5-trichloro-phenyl,4-iodo-3,5-dichlorophenyl, 3,4-dichloro-5-trifluoromethylphenyl,4-chloro-3,5-bis-(trifluoromethyl)-phenyl, most preferably R² is3,5-dichloro-phenyl.

Preferably each R³ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl, C₁-C₈alkoxy orC₁-C₈haloalkoxy, or two R′ on adjacent carbon atoms together form a—CH═CH—CH═CH— bridge, more preferably halogen, cyano, nitro, C₁-C₈alkyl,C₂-C₈ alkenyl, C₃-C₈cycloalkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy orC₁-C₈haloalkoxy, even more preferably bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, cyclopropyl, vinyl, methoxy,trifluoromethoxy, yet even more preferably bromo, chloro, fluoro,cyclopropyl, trifluoromethyl, vinyl, or methyl, ethyl, nitro, cyano,most preferably bromo, chloro, fluoro, or methyl.

Preferably each R⁴ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, more preferably iodo,bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl,methoxy, difluoromethoxy, or trifluoromethoxy, most preferably bromo,chloro, fluoro, iodo or trifluoromethyl.

The compounds of formula IA and IB have a lower than expected log Pvalue potentially leading to increased bioavailability.

Compounds of formula IA include at least one chiral centre and may existas compounds of formula IA* or compounds of formula IA**. Compounds IA*and IA** are enantiomers if there is no other chiral center or epimersotherwise.

Compounds of formula IA** are more biologically active than compounds offormula IA*. The invention includes mixtures of compounds IA* and IA**in any ratio e.g. in a molar ratio of 1:99 to 99:1, e.g. 10:1 to 1:10,e.g. a substantially 50:50 molar ratio. In an enantiomerically (orepimerically) enriched mixture of formula IA**, the molar proportion ofcompound IA** compared to the total amount of both IA* and IA** is forexample greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (orepimerically) enriched mixture of formula IA*, the molar proportion ofthe compound of formula IA* compared to the total amount of IA* and IA**is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80,85, 90, 95, 96, 97, 98, or at least 99%. Enantiomerically (orepimerically) enriched mixtures of formula IA** are preferred.

Likewise, compounds of formula IB include at least one chiral centre andmay exist as compounds of formula IB* or compounds of formula IB**.Compounds IB* and IB** are enantiomers if there is no other chiralcenter or epimers otherwise.

Compounds of formula IB** are more biologically active than compounds offormula IB*. The invention includes mixtures of compounds IB* and IB**in any ratio e.g. in a molar ratio of 1:99 to 99:1, e.g. 10:1 to 1:10,e.g. a substantially 50:50 molar ratio. In an enantiomerically (orepimerically) enriched mixture of formula IB**, the molar proportion ofcompound IB** compared to the total amount of both IB* and IB** is forexample greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or at least 99%. Likewise, in enantiomerically (orepimerically) enriched mixture of formula IB*, the molar proportion ofthe compound of formula IB* compared to the total amount of IB* and IB**is for example greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80,85, 90, 95, 96, 97, 98, or at least 99%. Enantiomerically (orepimerically) enriched mixtures of formula IB** are preferred.

The present invention includes all isomers of compounds of formula IAand IB, salts and N-oxides thereof, including enantiomers, diastereomersand tautomers. The compound of formula IA or IB may be a mixture of anytype of isomer or may be substantially a single type of isomer. Forexample, where Y¹ or Y² is SO, the SO may be a mixture of the cis andtrans isomer in any ratio, e.g. in a molar ratio of 1:99 to 99:1, e.g.10:1 to 1:10, e.g. a substantially 50:50 molar ratio. For example, intrans enriched mixtures of the compound of formula IA or IB, e.g. whenY¹ or Y² is SO, the molar proportion of the trans compound in themixture compared to the total amount of both cis and trans is forexample greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or at least 99%. Likewise, in cis enriched mixtures ofthe compound of formula IA or IB (cis enriched mixtures are preferred),e.g. when Y¹ or Y² is SO, the molar proportion of the cis compound inthe mixture compared to the total amount of both cis and trans is forexample greater than 50%, e.g. at least 55, 60, 65, 70, 75, 80, 85, 90,95, 96, 97, 98, or at least 99%. The compound of formula IA or IB may beenriched for the trans sulphoxide. Likewise, the compound of formula IAor IB may be enriched for the cis sulphoxide.

Further details regarding the process steps are given below.

1) Compounds of formula (I) (i.e. compound of formula IA and IB) can beprepared by reacting a compound of formula (V) wherein R is OH,C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (XVI), wherein L ismethylene or ethylene, as shown in Scheme 1. When R is OH such reactionsare usually carried out in the presence of a coupling reagent, such asN,N′-dicyclohexylcarbodiimide (“DCC”),1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride (“EDC”) orbis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-CI”), in the presenceof a base, and optionally in the presence of a nucleophilic catalyst,such as hydroxybenzotriazole (“HOBT”). When R is Cl, such reactions areusually carried out in the presence of a base, and optionally in thepresence of a nucleophilic catalyst. It is possible to conduct thereaction in a biphasic system comprising an organic solvent, preferablyethyl acetate, and an aqueous solvent, preferably a solution of sodiumhydrogen carbonate. When R is C₁-C₆alkoxy it is sometimes possible toconvert the ester directly to the amide by heating the ester and aminetogether in a thermal process. Suitable bases include pyridine,triethylamine, 4-(dimethylamino)-pyridine (“DMAP”) ordiisopropylethylamine (Hunig's base). Preferred solvents areN,N-dimethylacetamide, tetrahydrofuran, dioxane, 1,2-dimethoxyethane,ethyl acetate and toluene. The reaction is carried out at a temperatureof from 0° C. to 100° C., preferably from 15° C. to 30° C., inparticular at ambient temperature. Amines of formula (XVI) are eitherknown in the literature or can be prepared using methods known to aperson skilled in the art. Some of these methods are described in thepreparation examples.

2) Acid halides of formula (V), wherein R is Cl, F or Br, may be madefrom carboxylic acids of formula (V), wherein R is OH, under standardconditions, as described for example in WO2008/128711.

3) Carboxylic acids of formula (V), wherein R is OH, may be formed fromesters of formula (V), wherein R is C₁-C₆alkoxy as described for examplein WO2009/072621.

4) Compounds of formula (I) wherein, can be prepared by reacting acompound of formula (VI) wherein X^(B) is a leaving group, for example ahalogen, such as bromo, with carbon monoxide and an amine of formula(XVI), in the presence of a catalyst, such as palladium(II) acetate orbis-(triphenylphosphine)palladium(II) dichloride, optionally in thepresence of a ligand, such as triphenylphosphine, and a base, such assodium carbonate, pyridine, triethylamine, 4-(dimethylamino)-pyridine(“DMAP”) or diisopropylethylamine (Hunig's base), in a solvent, such aswater, N,N-dimethylformamide or tetrahydrofuran. The reaction is carriedout at a temperature from 50° C. to 200° C., preferably from 100° C. to150° C. The reaction is carried out at a pressure from 50 to 200 bar,preferably from 100 to 150 bar.

-   -   5) Compounds of formula (VI) wherein X^(B) is a leaving group,        e.g. halogen, C₁-C₈alkoxy, C₁-C₈alkylsulfonyloxy,        C₁-C₈haloalkylsulfonyloxy, C₁-C₈arylsulfonyloxy, optionally        substituted C₁-C₈arylsulfonyloxy (aryl is preferably phenyl),        diazonium salts (e.g. X^(B) is —N₂ ⁺Cl⁻, —N₂ ⁺BF₄ ⁻, —N₂ ⁺Br,        —N₂ ⁺PF₆ ⁻), phosphonate esters (e.g. —OP(O)(ORx)₂, wherein Rx        is methyl or ethyl), preferably bromo, iodo, chloro,        trifluoromethylsulfoxy, p-toluenesulfoxy, diazonium chloride,        preferably halogen, more preferably bromo, can be made by a        various of methods, for example as described in WO2009/080250.

6) Thietan-3-nitrile (III) can be obtained by reaction ofepithiochlorhydrin (II) with a cyanide M-CN, such as sodium cyanide orpotassium cyanide in the presence of water, preferably as a co-solventwith an organic solvent such as benzene or tetrahydrofuran, at atemperature of 20° C. to 100° C., preferably 40-60° C. preferably around50° C. Water is preferably used as a solvent, more preferably as aco-solvent with an organic solvent, preferably a water-immiscibleorganic solvent, e.g. such that the reaction then takes place in abiphasic system. The organic co-solvent is preferred to be aprotic, andis more preferably chosen from pentane, hexane, heptane, cyclohexane,benzene, toluene, xylene, tetrahydrofuran, ethyl acetate, diethyl ether,or methyl-tert-butyl ether. The reaction can be performed with an excessof epithiochlorhydrin or with an excess of M-CN, preferably instoechiometric ratio or slight excess of one or the other reagent.

7) Compounds of formula (IV) can be prepared by reaction of compounds offormula (III) with a suitable reducing reagent. The most suitable, butnot exclusive, method is the use of metal hydride reagents, such aslithium aluminum hydride or borane, in the presence or not ofcocatalysts. Other methods that can be carried out involve thehydrogenation in the presence of Raney Ni, or palladium for instance.The most common solvents for this reaction are alcohols such as methanolor ethanol, tetrahydrofuran, toluene, ethers, such as diethyl ether ormethyl tert-butyl ether. In most cases it is advantageous to conduct thereaction at dilution between 0.1 M to 1 M, preferably 0.3 M to 0.5 M, ata temperature of 0° C. to 100° C., preferably 0-80° C. preferably around20° C., and the reaction time in most cases is between 30 minutes and 12hours.

8) Compounds of formula (VIII) can be obtained by various methods fromthe thietanone (VII). For example, they can be prepared by performing awittig reaction or a related reaction, using(triphenylphosphoranylidene)acetonitrile or(Cyanomethyl)diethoxyphosphine oxide as a reagent or following aprocedure in analogy to the one described in Organic Letters 2010,12(9), 1944-1947 and Journal of the American Chemical Society 2009,131(8), 2786-2787. Such reactions are usually performed in a solvent,such as toluene or dichloromethane, at a temperature of from 0° C. to150° C., preferably from 0° C. to 50° C. Thietan-3-one (VII) can beprepared according to known methods, for example described in Synlett,(11), 783-4; 1991 or in WO 2007046548.

9) Compounds of formula (IX) can be prepared by reaction of compounds offormula (VIII) with a suitable reducing reagent. The most suitable, butnot exclusive, method is the use of metal hydride reagents, such assodium borohydride. Other methods that can be carried out involve thehydrogenation under a hydrogen atmosphere in the presence of palladiumfor instance. The most common solvents for this reaction are alcoholssuch as methanol or ethanol. In most cases it is advantageous to conductthe reaction at dilution between 0.1 M to 1 M, preferably 0.3 M to 0.5M, at a temperature of 0° C. to 100° C., preferably 0-80° C. preferablyaround 20° C., and the reaction time in most cases is between 30 minutesand 12 hours.

10) Compounds of formula (X) can be prepared by reaction of compounds offormula (IX) with a suitable reducing reagent. The most suitable, butnot exclusive, method is the use of metal hydride reagents, such aslithium aluminum hydride or borane, in the presence or not ofcocatalysts. Other methods that can be carried out involve thehydrogenation in the presence of Raney Ni, or palladium for instance.The most common solvents for this reaction are alcohols such as methanolor ethanol, tetrahydrofuran, toluene, ethers, such as diethyl ether ormethyl tert-butyl ether. In most cases it is advantageous to conduct thereaction at dilution between 0.1 M to 1 M, preferably 0.3 M to 0.5 M, ata temperature of 0° C. to 100° C., preferably 0-80° C. preferably around20° C., and the reaction time in most cases is between 30 minutes and 12hours.

11) Alternatively, compounds of formula (X) may be obtained directly byreduction of compounds of formula (VIII), for example underhydrogenation conditions, e.g. using hydrogen and a metal hydrogenationcatalyst, e.g. Palladium, Rhodium, or Platinum.

Schemes 4 and 5 represent additional routes for the preparation of theamines.

12) Compound (IV) may be prepared by reduction of a nitromethylenecompound of formula (XI). Reducing agents suitable for this reductioninclude for example metal hydride reagents such as sodium borohydride orlithium aluminium hydride optionally in the presence of a catalyst, forexample nickel chloride. Hydrogenation in the presence of metal catalystsuch as raney nickel or palladium on charcoal is an alternative for suchreductions. Examples of such methods can be found in Journal of theAmerican Chemical Society (2003), 125(40), 12125-12136, US patent no20050261327, or in Journal of Medicinal Chemistry (2010), 53(7),2942-2951.

13) Compounds of formula (XI) can be prepared by reaction of the ketoneof formula (VII) with nitromethane under standard conditions (Henryreaction), as described for example in Angewandte Chemie, InternationalEdition, 45(46), 7736-7739; 2006 or in Journal of Medicinal Chemistry,53(8), 3227-3246; 2010.

14) Alternatively, the amine of formula (IV) may be obtained from thecarboxylic acid of formula (XIII) using Schmidt or Curtiusrearrangement. Schmidt rearrangement involves treatment with hydrazoicacid under a range of possible conditions known to the person skilled ofthe art, for example as described in Journal of Organic Chemistry,58(6), 1372-6; 1993 for the conversion ofbicyclo[1.1.1]pentane-2-carboxylic acid tobicyclo[1.1.1]pentane-2-amine. Curtius rearrangement can be carried outunder different possible conditions known to the person skilled in theart, for example treatment of (XIII) with diphenylphosphoryl azidefollowed by heating and reaction with an alcohol such as benzyl alcoholor tert-butanol; the corresponding ester is obtained and subsequentlydeprotected to the amine by hydrogenolysis (benzyl ester) or treatmentwith trifluoroacetic acid (tert-butyl ester). Such conditions are forexample described in Journal of Organic Chemistry, 75(17), 5941-5952,2010 or Tetrahedron: Asymmetry, 14(23), 3773-3778; 2003.

15) The acid of formula (XIII) may derive from the ketone of formula(VII) after homologation of the ketone (VII) to an ester of formula(XII) (wherein R is C₁-C₆alkyl) followed by hydride reduction orhydrogenation of the double bond. Similar synthetic sequences fromrelated substrates are described for example in Chemical &Pharmaceutical Bulletin, 52(6), 675-687; 2004, Synlett (2005), (10),1559-1562, WO 2005019221, or WO 2010031735.

16) Amines of formula (IV) and (X) may be converted to further amineintermediates of formula (XIV) and (XV) wherein n is 1 or 2. The aminesmay be directly oxidized or first protected, oxidized and thendeprotected

Compounds XIV and XV form further aspects of the invention.

The compounds according to the present invention show a potentialinseciticidal action and can therefore be used as an insecticide.Furthermore, the compounds according to the present invention canexhibit a strong control effect against harmful insects, withoutsubstantially imposing any harmful side effects to cultivated plants.The compounds of the present invention can thus be used for the controlof a wide range of pest species, for example, harmful sucking insects,chewing insects, as well as other plant parasitic pests, storageinsects, hygiene pests and the like, and can be applied for the purposeof disinfestations and extermination thereof.

Harmful animal pest are for example:

As for insects, coleopterans, for example, Callosobruchus chinensis,Sitophilus zeamais, Tribolium castaneum, Epilachna vigintioctomaculata,Agriotes fuscicollis, Anomala rufocuprea, Leptinotarsa decemlineata,Diabrotica spp., Monochamus alternatus, Lissorhoptrus oryzophilus,Lyctus bruneus, Aulacophora femoralis; lepidopterans, for example,Lymantria dispar, Malacosoma neustria), Pieris rapae, Spodoptera litura,Mamestra brassicae, Chilo suppressalis), Pyrausta nubilalis, Ephestiacautella, Adoxophyes orana, Carpocapsa pomonella, Agrotisfucosa,Galleria mellonella, Plutella maculipennis, Heliothis virescens,Phyllocnistis citrella; hemipterans, for example, Nephotettixcincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspisyanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Rhopalosiphumpseudobrassicas, Stephanitis nashi, Nezara spp., Trialeurodesvaporariorm, Psylla spp.; thysanopterans, for example, Thrips palmi,Franklinella occidental; orthopterans, for example, Blatella germanica,Periplaneta americana, Gryllotalpa Africana, Locusta migratoriamigratoriodes; isopterans, for example, Reticulitermes speratus,Coptotermes formosanus; dipterans, for example, Musca domestica, Aedesaegypti, Hylemia platura, Culex pipiens, Anopheles sinensis, Culextritaeniorhynchus, Liriomyza trifolii.

As for acari, for example, Tetranychus cinnabarinus, Tetranychusurticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp.

As for nematodes, for example, Meloidogyne incognita, Bursaphelenchuslignicolus Mamiya et Kiyohara, Aphelenchoides besseyi, Heteroderaglycines, Pratylenchus spp.

Additionally, the compounds according to the present invention may showa good plant tolerance and favourable toxicity to warm-blooded animalsand being tolerated well by the environment, and thus are suitable forprotecting plants and plant parts. Application of the compounds of theinvention may result in increasing the harvest yields, improving thequality of the harvested material.

Additionally, the compounds can be used for controlling animal pests, inparticular insects, arachnids, helminths, nematodes and molluscs, whichare encountered in agriculture, in horticulture, the field of veterinarymedicine, in forests, in gardens and leisure facilities, in theprotection of stored products and of materials, and in the hygienesector. They may preferably be employed as plant protection agents. Theymay be active against normally sensitive and resistant species andagainst all or some stages of development.

These pests include inter alia:

From the order of the Anoplura (Phthiraptera), for example, Damaliniaspp., Haematopinus spp., Linognathus spp., Pediculus spp., Trichodectesspp.

From the class of the Arachnida, for example, Acarus siro, Aceriasheldoni, Aculops spp., Aculus spp., Amblyomma spp., Argas spp.,Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Chorioptes spp.,Dermanyssus gaffinae, Eotetranychus spp., Epitrimerus pyri,Eutetranychus spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma spp.,Ixodes spp., Latrodectus mactans, Metatetranychus spp., Oligonychusspp., Ornithodoros spp., Panonychus spp., Phyllocoptruta oleivora,Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp.,Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Stenotarsonemus spp.,Tarsonemus spp., Tetranychus spp., Vasates lycopersici.

From the class of the Bivalve, for example, Dreissena spp.

From the order of the Chilopoda, for example, Geophilus spp., Scutigeraspp.

From the order of the Coleoptera, for example, Acanthoscehdes obtectus,Adoretus spp., Agelastica alni, Agriotes spp., Amphimallon solstitialis,Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp.,Apogonia spp., Atomaria spp., Attagenus spp., Bruchidius obtectus,Bruchus spp., Ceuthorhynchus spp., Cleonus mendicus, Conoderus spp.,Cosmopolites spp., Costelytra zealandica, Curculio spp., Cryptorhynchuslapathi, Dermestes spp., Diabrotica spp., Epilachna spp., Faustinuscubae, Gibbium psylloides, Heteronychus arator, Hylamorpha elegans,Hylotrupes bajulus, Hypera postica, Hypothenemus spp., Lachnosternaconsanguinea, Leptinotarsa decemlineata, Lissorhoptrus oryzophilus,Lixus spp., Lyctus spp., Meligethes aeneus, Melolontha melolontha,Migdolus spp., Monochamus spp., Naupactus xanthographus, Niptushololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Otiorrhynchussulcatus, Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp.,Popillia japonica, Premnotrypes spp., Psyffiodes chrysocephala, Ptinusspp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp.,Sphenophorus spp., Sternechus spp., Symphyletes spp., Tenebrio molitor,Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrusspp.

From the order of the Collembola, for example, Onychiurus armatus.

From the order of the Dermaptera, for example, Forficula auricularia.

From the order of the Diplopoda, for example, Blaniulus guttulatus.

From the order of the Diptera, for example, Aedes spp., Anopheles spp.,Bibio hortulanus, Calliphora erythrocephala, Ceratitis capitata,Chrysomyia spp., Cochliomyia spp., Cordylobia anthropophaga, Culex spp.,Cuterebra spp., Dacus oleae, Dermatobia hominis, Drosophila spp., Fanniaspp., Gastrophilus spp., Hylemyia spp., Hyppobosca spp., Hypoderma spp.,Liriomyza spp., Lucilia spp., Musca spp., Nezara spp., Oestrus spp.,Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Stomoxys spp., Tabanusspp., Tannia spp., Tipula paludosa, Wohlfahrtia spp.

From the class of the Gastropoda, for example, Anion spp., Biomphalariaspp., Bulinus spp., Deroceras spp., Galba spp., Lymnaea spp.,Oncomelania spp., Succinea spp.

From the class of the helminths, for example, Ancylostoma duodenale,Ancylostoma ceylanicum, Acylostoma braziliensis, Ancylostoma spp.,Ascaris lumbricoides, Ascaris spp., Brugia malayi, Brugia timori,Bunostomum spp., Chabertia spp., Clonorchis spp., Cooperia spp.,Dicrocoelium spp, Dictyocaulus filaria, Diphyllobothrium latum,Dracunculus medinensis, Echinococcus granulosus, Echinococcusmultilocularis, Enterobius vermicularis, Faciola spp., Haemonchus spp.,Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa Loa,Nematodirus spp., Oesophagostomum spp., Opisthorchis spp., Onchocercavolvulus, Ostertagia spp., Paragonimus spp., Schistosomen spp.,Strongyloides fuelleborni, Strongyloides stercoralis, Stronyloides spp.,Taenia saginata, Taenia solium, Trichinella spiralis, Trichinellanativa, Trichinella britovi, Trichinella nelsoni, Trichinellapseudopsiralis, Trichostrongulus spp., Trichuris trichiura, Wuchereriabancrofti.

It may be furthermore possible to control protozoa, such as Eimeria.

From the order of the Heteroptera, for example, Anasa tristis,Antestiopsis spp., Blissus spp., Calocoris spp., Campylomma livida,Cavelerius spp., Cimex spp., Creontiades dilutus, Dasynus piperis,Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistusspp., Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisaspp., Leptoglossus phyllopus, Lygus spp., Macropes excavatus, Miridae,Nezara spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp.,Psallus seriatus, Pseudacysta persea, Rhodnius spp., Sahlbergellasingularis, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatomaspp.

From the order of the Homoptera, for example, Acyrthosipon spp.,Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurolobusbarodensis, Aleurothrixus spp., Amrasca spp., Anuraphis cardui,Aonidiella spp., Aphanostigma piri, Aphis spp., Arboridia apicalis,Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani,Bemisia spp., Brachycaudus helichrysii, Brachycolus spp., Brevicorynebrassicae, Calligypona marginata, Carneocephala fulgida, Ceratovacunalanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii,Chionaspis tegalensis, Chlorita onukii, Chromaphis juglandicola,Chrysomphalus ficus, Cicadulina mbila, Coccomytilus haffi, Coccus spp.,Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp.,Diaspis spp., Doralis spp., Drosicha spp., Dysaphis spp., Dysmicoccusspp., Empoasca spp., Eriosoma spp., Erythroneura spp., Euscelisbilobatus, Geococcus coffeae, Homalodisca coagulata, Hyalopterusarundinis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelphaxstriatellus, Lecanium spp., Lepidosaphes spp., Lipaphis erysimi,Macrosiphum spp., Mahanarva fimbriolata, Melanaphis sacchari,Metcalfiella spp., Metopolophium dirhodum, Moneffia costalis,Moneffiopsis pecanis, Myzus spp., Nasonovia ribisnigri, Nephotettixspp., Nilaparvata lugens, Oncometopia spp., Orthezia praelonga,Parabemisia myricae, Paratrioza spp., Parlatoria spp., Pemphigus spp.,Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodonhumuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp.,Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcusspp., Psylla spp., Pteromalus spp., Pyrilla spp., Quadraspidiotus spp.,Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., Saissetia spp.,Scaphoides titanus, Schizaphis graminum, Selenaspidus articulatus,Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina,Tenalaphara malayensis, Tinocallis caryaefoliae, Tomaspis spp.,Toxoptera spp., Trialeurodes vaporariorum, Trioza spp., Typhlocyba spp.,Unaspis spp., Viteus vitifolii.

From the order of the Hymenoptera, for example, Diprion spp., Hoplocampaspp., Lasius spp., Mono-morium pharaonis, Vespa spp.

From the order of the Isopoda, for example, Armadiffidium vulgare,Oniscus asellus, Porceffio scaber.

From the order of the Isoptera, for example, Reticulitermes spp.,Odontotermes spp.

From the order of the Lepidoptera, for example, Acronicta major, Aedialeucomelas, Agrotis spp., Alabama argillacea, Anticarsia spp., Barathrabrassicae, Bucculatrix thurberiella, Bupalus piniarius, Cacoecia podana,Capua reticulana, Carpocapsa pomonella, Cheimatobia brumata, Chilo spp.,Choristoneura fumiferana, Clysia ambiguella, Cnaphalocerus spp., Eariasinsulana, Ephestia kuehniella, Euproctis chrysorrhoea, Euxoa spp.,Feltia spp., Galleria mellonella, Helicoverpa spp., Heliothis spp.,Hofmannophila pseudospretella, Homona magnanima, Hyponomeuta padella,Laphygma spp., Lithocolletis blancardella, Lithophane antennata,Loxagrotis albicosta, Lymantria spp., Malacosoma neustria, Mamestrabrassicae, Mocis repanda, Mythimna separata, Oria spp., Oulema oryzae,Panolis flammea, Pectinophora gossypiella, Phyllocnistis citrella,Pieris spp., Plutella xylostella, Prodenia spp., Pseudaletia spp.,Pseudoplusia includens, Pyrausta nubilalis, Spodoptera spp., Thermesiagemmatalis, Tinea pellionella, Tineola bisselliella, Tortrix viridana,Trichoplusia spp.

From the order of the Orthoptera, for example, Acheta domesticus, Blattaorientalis, Blattella germanica, Gryllotalpa spp., Leucophaea maderae,Locusta spp., Melanoplus spp., Periplaneta americana, Schistocercagregaria.

From the order of the Siphonaptera, for example, Ceratophyllus spp.,Xenopsylla cheopis.

From the order of the Symphyla, for example, Scutigerella immaculata.

From the order of the Thysanoptera, for example, Baliothrips biformis,Enneothrips flavens, Frankliniella spp., Heliothrips spp., Hercinothripsfemoralis, Kakothrips spp., Rhipiphorothrips cruentatus, Scirtothripsspp., Taeniothrips cardamoni, Thrips spp.

From the order of the Thysanura, for example, Lepisma saccharina.

The phytoparasitic nematodes include, for example, Anguina spp.,Aphelenchoides spp., Belonoaimus spp., Bursaphelenchus spp., Ditylenchusdipsaci, Globodera spp., Heliocotylenchus spp., Heterodera spp.,Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radopholussimilis, Rotylenchus spp., Trichodorus spp., Tylenchorhynchus spp.,Tylenchulus spp., Tylenchulus semipenetrans, Xiphinema spp.

All plants and plant parts can be treated in accordance with theinvention.

Plants are to be understood as meaning in the present context all plantsand plant populations such as desired and undesired wild plants or cropplants (including naturally occurring crop plants).

Crop plants can be plants which can be obtained by conventional plantbreeding and optimization methods or by biotechnological and geneticengineering methods or by combinations of these methods, including thetransgenic plants and including the plant cultivars protectable or notprotectable by plant breeders' rights.

Plant parts are to be understood as meaning all parts and organs ofplants above and below the ground, such as shoot, leaf, flower and root,examples which may be mentioned being leaves, needles, stalks, stems,flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.

The plant parts also include harvested material, and vegetative andgenerative propagation material, for example cuttings, tubers, rhizomes,offshoots and seeds. Treatment according to the invention of the plantsand plant parts with the active compounds is carried out directly or byallowing the compounds to act on their surroundings, habitat or storagespace by the customary treatment methods, for example by immersion,spraying, evaporation, fogging, scattering, painting on, injecting and,in the case of propagation material, in particular in the case of seed,also by applying one or more coats.

In a preferred embodiment, wild plant species and plant cultivars, orthose obtained by conventional biological breeding methods, such ascrossing or protoplast fusion, and parts thereof, are treated.

In a further preferred embodiment, transgenic plants and plant cultivarsobtained by genetic engineering methods, if appropriate in combinationwith conventional methods (Genetically Modified Organisms), and partsthereof, are treated. Particularly preferably, plants of the plantcultivars which are in each case commercially available or in use aretreated according to the invention. Plant cultivars are understood asmeaning plants having novel properties (“traits”) which have beenobtained by conventional breeding, by mutagenesis or by recombinant DNAtechniques.

These can be cultivars, bio- or genotypes. Depending on the plantspecies or plant cultivars, their location and growth conditions (soils,climate, vegetation period, diet), the treatment according to theinvention may also result in superadditive “synergistic”) effects.

Thus, for example, reduced application rates and/or a widening of theactivity spectrum and/or an increase in the activity of the substancesand compositions which can be used according to the invention, betterplant growth, increased tolerance to high or low temperatures, increasedtolerance to drought or to water or soil salt content, increasedflowering performance, easier harvesting, accelerated maturation, higherharvest yields, higher quality and/or a higher nutritional value of theharvested products, better storage stability and/or processability ofthe harvested products are possible, which exceed the effects which wereactually to be expected.

The preferred transgenic plants or plant cultivars (obtained by geneticengineering) which are to be treated according to the invention includeall plants which, by virtue of the genetic modification, receivedgenetic material which imparts particularly advantageous, useful traitsto these plants. Examples of such traits are better plant growth,increased tolerance to high or low temperatures, increased tolerance todrought or to water or soil salt content, increased floweringperformance, easier harvesting, accelerated maturation, higher harvestyields, higher quality and/or a higher nutritional value of theharvested products, better storage stability and/or processability ofthe harvested products.

Further and particularly emphasized examples of such traits are a betterdefence of the plants against animal and microbial pests, such asagainst insects, mites, phytopathogenic fungi, bacteria and/or viruses,and also increased tolerance of the plants to certain herbicidallyactive compounds.

Examples of transgenic plants which may be mentioned are the importantcrop plants, such as cereals (wheat, rice), maize, soya beans, potatoes,sugar beet, tomatoes, peas and other vegetable varieties, cotton,tobacco, oilseed rape and also fruit plants (with the fruits apples,pears, citrus fruits and grapes), and particular emphasis is given tomaize, soya beans, potatoes, cotton, tobacco and oilseed rape.

Traits that are emphasized in particular are the increased defence ofthe plants against insects, arachnids, nematodes and slugs and snails byvirtue of toxins formed in the plants, in particular those formed in theplants by the genetic material from Bacillus thuringiensis (for exampleby the genes CryIA(a), CryIA(b), CryIA(c), CryIIA, CryIIIA, CryIIIB2,Cry9c, Cry2Ab, Cry3Bb and CryIF and also combinations thereof) (referredto hereinbelow as “Bt plants”).

Traits that are also particularly emphasized are the increased defenceof the plants against fungi, bacteria and viruses by systemic acquiredresistance (SAR), systemin, phytoalexins, elicitors and resistance genesand correspondingly expressed proteins and toxins.

Traits that are furthermore particularly emphasized are the increasedtolerance of the plants to certain herbicidally active compounds, forexample imidazolinones, sulphonylureas, glyphosate or phosphinotricin(for example the “PAT” gene). The genes which impart the desired traitsin question can also be present in combination with one another in thetransgenic plants.

Examples of “Bt plants” which may be mentioned are maize varieties,cotton varieties, soya bean varieties and potato varieties which aresold under the trade names YIELD GARD® (for example maize, cotton, soyabeans), KnockOut® (for example maize), StarLink® (for example maize),Bollgard® (cotton), Nucotn® (cotton) and NewLeaf® (potato).

Examples of herbicide-tolerant plants which may be mentioned are maizevarieties, cotton varieties and soya bean varieties which are sold underthe trade names Roundup Ready® (tolerance to glyphosate, for examplemaize, cotton, soya beans), Liberty Link® (tolerance to phosphinotricin,for example oilseed rape), IMI® (tolerance to imidazolinones) and STS®(tolerance to sulphonylureas, for example maize).

Herbicide-resistant plants (plants bred in a conventional manner forherbicide tolerance) which may be mentioned include the varieties soldunder the name Clearfield® (for example maize).

These statements also apply to plant cultivars having these genetictraits or genetic traits still to be developed, which plant cultivarswill be developed and/or marketed in the future.

The plants listed can be treated according to the invention in aparticularly advantageous manner with the compounds according to theinvention at a suitable concentration.

Furthermore, in the field of veterinary medicine, the novel compounds ofthe present invention can be effectively used against various harmfulanimal parasitic pests (endoparasites and ectoparasites), for example,insects and helminthes.

Examples of such animal parasitic pests include the pests as describedbelow.

Examples of the insects include Gasterophilus spp., Stomoxys spp.,Trichodectes spp., Rhodnius spp., Ctenocephalides canis, Cimx lecturius,Ctenocephalides fells, Lucilia cuprina, and the like.

Examples of acari include Ornithodoros spp., Ixodes spp., Boophilusspp., and the like.

In the veterinary fields, e.g. in the field of veterinary medicine, theactive compounds according to the present invention are active againstanimal parasites, in particular ectoparasites or endoparasites.

The term endoparasites includes in particular helminths, such ascestodes, nematodes or trematodes, and protozoae, such as coccidia.

Ectoparasites are typically and preferably arthropods, in particularinsects such as flies (stinging and licking), parasitic fly larvae,lice, hair lice, bird lice, fleas and the like; or acarids, such asticks, for examples hard ticks or soft ticks, or mites, such as scabmites, harvest mites, bird mites and the like.

These parasites include:

From the order of the Anoplurida, for example Haematopinus spp.,Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.;particular examples are: Linognathus setosus, Linognathus vituli,Linognathus ovillus, Linognathus oviformis, Linognathus pedalis,Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinuseurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculushumanus corporis, Phylloera vastatrix, Phthirus pubis, Solenopotescapillatus; from the order of the Mallophagida and the subordersAmblycerina and lschnocerina, for example Trimenopon spp., Menopon spp.,Trinoton spp., Bovicola spp., Werneckiella spp., Lepikentron spp.,Damalina spp., Trichodectes spp., Felicola spp.; particular examplesare: Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis,Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentronovis, Werneckiella equi; from the order of the Diptera and the subordersNematocerina and Brachycerina, for example Aedes spp., Anopheles spp.,Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyiaspp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp.,Hybomitra spp., Atylotus spp., Tabanus spp., Haematopota spp.,Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxysspp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp.,Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp.,Sarcophaga spp., Oestrus spp., Hypoderma spp., Gasterophilus spp.,Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp.,Tipula spp.; particular examples are: Aedes aegypti, Aedes albopictus,Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis,Calliphora erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus,Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria,Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata,Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmiaornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius,Tabanus spodopterus, Tabanus atratus, Tabanus sudeticus, Hybomitraciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis,Haematopota italica, Musca autumnalis, Musca domestica, Haematobiairritans irritans, Haematobia irritans exigua, Haematobia stimulans,Hydrotaea irritans, Hydrotaea albipuncta, Chrysomya chloropyga,Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum,Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptenacapreoli, Lipoptena cervi, Hippobosca variegata, Hippobosca equina,Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gasterophilusinermis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophiluspecorum, Braula coeca; from the order of the Siphonapterida, for examplePulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp.,Ceratophyllus spp.; particular examples are: Ctenocephalides canis,Ctenocephalides fells, Pulex irritans, Tunga penetrans, Xenopsyllacheopis; from the order of the Heteropterida, for example Cimex spp.,Triatoma spp., Rhodnius spp., Panstrongylus spp.

From the order of the Blattarida, for example Blatta orientalis,Periplaneta americana, Blattela germanica, Supella spp. (e.g. Suppellalongipalpa);

From the subclass of the Acari (Acarina) and the orders of the Meta- andMesostigmata, for example Argas spp., Ornithodorus spp., Otobius spp.,Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp Dermacentorspp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalusspp. (the original genus of multi host ticks) Ornithonyssus spp.,Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp.,Varroa spp., Acarapis spp.; particular examples are: Argas persicus,Argas reflexus, Ornithodorus moubata, Otobius megnini, Rhipicephalus(Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus,Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus)calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalommamarginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus,Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubicundus,Ixodes scapularis, Ixodes holocyclus, Haemaphysalis concinna,Haemaphysalis punctata, Haemaphysalis cinnabarina, Haemaphysalisotophila, Haemaphysalis leachi, Haemaphysalis longicomi, Dermacentormarginatus, Dermacentor reticulatus, Dermacentor pictus, Dermacentoralbipictus, Dermacentor andersoni, Dermacentor variabilis, Hyalommamauritanicum, Rhipicephalus sanguineus, Rhipicephalus bursa,Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalusturanicus, Rhipicephalus zambeziensis, Amblyomma americanum, Amblyommavariegatum, Amblyomma maculatum, Amblyomma hebraeum, Amblyommacajennense, Dermanyssus gaffinae, Ornithonyssus bursa, Ornithonyssussylviarum, Varroa jacobsoni; from the order of the Actinedida(Prostigmata) and Acaridida (Astigmata), for example Acarapis spp.,Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp.,Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp.,Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp.,Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp.,Notoedres spp., Knemidocoptes spp., Cytodites spp., Laminosioptes spp.;particular examples are: Cheyletiella yasguri, Cheyletiella blakei,Demodex canis, Demodex bovis, Demodex ovis, Demodex caprae, Demodexequi, Demodex cabaffi, Demodex suis, Neotrombicula autumnalis,Neotrombicula desaleri, Neoschongastia xerothermobia, Trombiculaakamushi, Otodectes cynotis, Notoedres cati, Sarcoptis canis, Sarcoptesbovis, Sarcoptes ovis, Sarcoptes rupicaprae (S. caprae), Sarcoptes equi,Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi,Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange,Pneumonyssoides caninum, Acarapis woodi.

The active compounds according to the invention are also suitable forcontrolling arthropods, helminths and protozoae, which attack animals.

Animals include agricultural livestock such as, for example, cattle,sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits,chickens, turkeys, ducks, geese, cultured fish, honeybees.

Moreover, animals include domestic animals—also referred to as companionanimals—such as, for example, dogs, cats, cage birds, aquarium fish andwhat are known as experimental animals such as, for example, hamsters,guinea pigs, rats and mice.

By controlling these arthropods, helminths and/or protozoae, it isintended to reduce deaths and improve performance (in the case of meat,milk, wool, hides, eggs, honey and the like) and health of the hostanimal, so that more economical and simpler animal keeping is madepossible by the use of the active compounds according to the invention.

For example, it may be desirable to prevent or interrupt the uptake ofblood by the parasites from the hosts.

Also, controlling the parasites may help to prevent the transmittance ofinfectious agents.

The term “controlling” as used herein with regard to the veterinaryfield, means that the active compounds are effective in reducing theincidence of the respective parasite in an animal infected with suchparasites to innocuous levels.

More specifically, “controlling”, as used herein, means that the activecompound is effective in killing the respective parasite, inhibiting itsgrowth, or inhibiting its proliferation. Generally, when used for thetreatment of animals the active compounds according to the invention canbe applied directly.

Preferably they are applied as pharmaceutical compositions which maycontain pharmaceutically acceptable excipients and/or auxiliaries whichare known in the art.

In the veterinary field and in animal keeping, the active compounds areapplied (e.g. administered) in the known manner by enteraladministration in the form of, for example, tablets, capsules, drinks,drenches, granules, pastes, boluses, the feed-through method,suppositories; by parenteral administration, such as, for example, byinjections (intramuscular, subcutaneous, intravenous, intraperitonealand the like), implants, by nasal application, by dermal application inthe form of, for example, bathing or dipping, spraying, pouring-on andspotting-on, washing, dusting, and with the aid ofactive-compound-comprising shaped articles such as collars, ear tags,tail tags, limb bands, halters, marking devices and the like.

The active compounds may be formulated as shampoo or as suitableformulations usable in aerosols, unpressurized sprays, for example pumpsprays and atomizer sprays.

When used for livestock, poultry, domestic animals and the like, theactive compounds according to the invention can be applied asformulations (for example powders, wettable powders [“WP”], emulsions,emulsifiable concentrates [“EC”], flowables, homogeneous solutions, andsuspension concentrates [“SC”]) which comprise the active compounds inan amount of from 1 to 80 percent by weight, either directly or afterdilution (e.g. 100- to 10 000-fold dilution), or else as a chemicalbath.

When used in the veterinary field the active compounds according to theinvention may be used in combination with suitable synergists or otheractive compounds, such as for example, acaricides, insecticides,anthelmintics, anti-protozoal drugs.

In the present invention, a substance having an insecticidal actionagainst pests including all of these is referred to as an insecticide.

An active compound of the present invention can be prepared inconventional formulation forms, when used as an insecticide.

Examples of the formulation forms include solutions, emulsions, wettablepowders, water dispersible granules, suspensions, powders, foams,pastes, tablets, granules, aerosols, active compound-infiltrated naturaland synthetic materials, microcapsules, seed coating agents,formulations used with a combustion apparatus (for example, fumigationand smoking cartridges, cans, coils or the like as the combustionapparatus), ULV (cold mist, warm mist), and the like.

These formulations can be produced by methods that are known per se.

For example, a formulation can be produced by mixing the active compoundwith a developer, that is, a liquid diluent or carrier; a liquefied gasdiluent or carrier; a solid diluent or carrier, and optionally with asurfactant, that is, an emulsifier and/or dispersant and/or foamingagent.

In the case where water is used as the developer, for example, anorganic solvent can also be used as an auxiliary solvent.

Examples of the liquid diluent or carrier include aromatic hydrocarbons(for example, xylene, toluene, alkylnaphthalene and the like),chlorinated aromatic or chlorinated aliphatic hydrocarbons (for example,chlorobenzenes, ethylene chlorides, methylene chlorides), aliphatichydrocarbons (for example, cyclohexanes), paraffins (for example,mineral oil fractions), alcohols (for example, butanol, glycols andtheir ethers, esters and the like), ketones (for example, acetone,methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone and thelike), strongly polar solvents (for example, dimethylformamide,dimethylsulfoxide and the like), water and the like. The liquefied gasdiluent or carrier may be those which are gaseous at normal temperatureand normal pressure, for example, aerosol propellants such as butane,propane, nitrogen gas, carbon dioxide and halogenated hydrocarbons.Examples of the solid diluent include pulverized natural minerals (forexample, kaolin, clay, talc, chalk, quartz, attapulgite,montmorillonite, diatomaceous earth, and the like), pulverized syntheticminerals (for example, highly dispersed silicic acid, alumina, silicatesand the like), and the like. Examples of the solid carrier for granulesinclude pulverized and screened rocks (for example, calcite, marble,pumice, sepiolite, dolomite and the like), synthetic granules ofinorganic and organic powder, fine particles of organic materials (forexample, sawdust, coconut shells, maize cobs, tobacco stalk and thelike), and the like. Examples of the emulsifier and/or foaming agentinclude nonionic and anionic emulsifiers [for example, polyoxyethylenefatty acid esters, polyoxyethylene fatty acid alcohol ethers (forexample, alkylaryl polyglycol ether), alkylsulfonates, alkylsulfates,arylsulfonates and the like], albumin hydro lyzate, and the like.Examples of the dispersant include lignin sulfite waste liquor andmethylcellulose.

Fixing agents can also be used in the formulations (powders, granules,emulsions), and examples of the fixing agent includecarboxymethylcellulose, natural and synthetic polymers (for example, gumarabic, polyvinyl alcohol, polyvinyl acetate, and the like) and thelike. Colorants can also be used, and examples of the colorants includeinorganic pigments (for example, iron oxide, titanium oxide, PrussianBlue and the like), organic dyes such as alizarin dyes, azo dyes ormetal phthalocyanine dyes, and in addition, trace elements such as thesalts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.The formulations in general can contain the active ingredient in anamount ranging from 0.1 to 95 percent by weight, and preferably 0.5 to90 percent> by weight. The compound according to the present inventioncan also exist as an admixture with other active compounds, for example,insecticides, poisonous baits, bactericides, miticides, nematicides,fungicides, growth regulators, herbicides and the like, in the form oftheir commercially useful formulation forms and in the application formsprepared from those formulations.

The content of the compound according to the present invention in acommercially useful application form can be varied within a wide range.

The concentration of the active compound according to the presentinvention in actual usage can be, for example, in the range of 0.0000001to 100 percent by weight, and preferably 0.00001 to 1 percent by weight.

The compounds according to the present invention can be used throughconventional methods that are appropriate for the usage form.

The active compound of the present invention have, when used againsthygiene pests and pests associated with stored products, stabilityeffective against alkali on lime materials, and also shows excellentresidual effectiveness on wood and soil. The compounds of the inventionmay have favourable properties with respect to amount applied, residueformulation, selectivity, toxicity, production methodology, highactivity, wide spectrum of control, safety, control of resistantorganisms, e.g. pests that are resistant to organic phosphorus agentsand/or carbamate agents.

Further embodiments of the invention are described below.

The compounds of formula (I) can be used to combat and controlinfestations of insect pests such as Lepidoptera, Diptera, Hemiptera,Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera,Hymenoptera and Isoptera and also other invertebrate pests, for example,acarine, nematode and mollusc pests. Insects, acarines, nematodes andmolluscs are hereinafter collectively referred to as pests. The pestswhich may be combated and controlled by the use of the inventioncompounds include those pests associated with agriculture (which termincludes the growing of crops for food and fiber products), horticultureand animal husbandry, companion animals, forestry and the storage ofproducts of vegetable origin (such as fruit, grain and timber); thosepests associated with the damage of man-made structures and thetransmission of diseases of man and animals; and also nuisance pests(such as flies).

The compounds of the invention may be used for example on turf,ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens,for example conifers, as well as for tree injection, pest management andthe like.

Examples of pest species which may be controlled by the compounds offormula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta_(—) migratoria (locust), Chortiocetes terminifera (locust), Diabroticaspp. (rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalides felis (cat flea),Liriomyza spp. (leaf miner), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotermitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulfureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand sucking lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp. (citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

The compounds of the invention may be used for pest control on variousplants, including soybean (e.g. in some cases 10-70 g/ha), corn (e.g. insome cases 10-70 g/ha), sugarcane (e.g. in some cases 20-200 g/ha),alfalfa (e.g. in some cases 10-70 g/ha), brassicas (e.g. in some cases10-50 g/ha), oilseed rape (e.g. canola) (e.g. in some cases 20-70 g/ha),potatoes (including sweet potatoes) (e.g. in some cases 10-70 g/ha),cotton (e.g. in some cases 10-70 g/ha), rice (e.g. in some cases 10-70g/ha), coffee (e.g. in some cases 30-150 g/ha), citrus (e.g. in somecases 60-200 g/ha), almonds (e.g. in some cases 40-180 g/ha), fruitingvegetables (e.g. tomatoes, pepper, chili, eggplant, cucumber, squashetc.) (e.g. in some cases 10-80 g/ha), tea (e.g. in some cases 20-150g/ha), bulb vegetables (e.g. onion, leek etc.) (e.g. in some cases 30-90g/ha), grapes (e.g. in some cases 30-180 g/ha), pome fruit (e.g. apples,pears etc.) (e.g. in some cases 30-180 g/ha), and stone fruit (e.g.pears, plums etc.) (e.g. in some cases 30-180 g/ha).

The compounds of the invention may be used on soybean to control, forexample, Elasmopalpus lignosellus, Diloboderus abderus, Diabroticaspeciosa, Sternechus subsignatus, Formicidae, Agrotis ipsilon, Julusssp., Anticarsia gemmatalis, Megascelis ssp., Procornitermes ssp.,Gryllotalpidae, Nezara viridula, Piezodorus spp., Acrosternum spp.,Neomegalotomus spp., Cerotoma trifurcata, Popillia japonica, Edessaspp., Liogenys fuscus, Euchistus heros, stalk borer, Scaptocoriscastanea, phyllophaga spp., Pseudoplusia includens, Spodoptera spp.,Bemisia tabaci, Agriotes spp. The compounds of the invention arepreferably used on soybean to control Diloboderus abderus, Diabroticaspeciosa, Nezara viridula, Piezodorus spp., Acrosternum spp., Cerotomatrifurcata, Popillia japonica, Euchistus heros, phyllophaga spp.,Agriotes spp.

The compounds of the invention may be used on corn to control, forexample, Euchistus heros, Dichelops furcatus, Diloboderus abderus,Elasmopalpus lignosellus, Spodoptera frugiperda, Nezara viridula,Cerotoma trifurcata, Popiffia japonica, Agrotis ipsilon, Diabroticaspeciosa, Heteroptera, Procornitermes ssp., Scaptocoris castanea,Formicidae, Julus ssp., Dalbulus maidis, Diabrotica virgifera, Mocislatipes, Bemisia tabaci, heliothis spp., Tetranychus spp., thrips spp.,phyllophaga spp., scaptocoris spp., Liogenys fuscus, Spodoptera spp.,Ostrinia spp., Sesamia spp., Agriotes spp. The compounds of theinvention are preferably used on corn to control Euchistus heros,Dichelops furcatus, Diloboderus abderus, Nezara viridula, Cerotomatrifurcata, Popffiia japonica, Diabrotica speciosa, Diabroticavirgifera, Tetranychus spp., thrips spp., phyllophaga spp., scaptocorisspp., Agriotes spp.

The compounds of the invention may be used on sugar cane to control, forexample, Sphenophorus spp., termites, Mahanarva spp. The compounds ofthe invention are preferably used on sugar cane to control termites,Mahanarva spp.

The compounds of the invention may be used on alfalfa to control, forexample, Hypera brunneipennis, Hypera postica, Collas eurytheme, Collopsspp., Empoasca solana, Epitrix, Geocoris spp., Lygus hesperus, Lyguslineolaris, Spissistilus spp, Spodoptera spp., Trichoplusia ni. Thecompounds of the invention are preferably used on alfalfa to controlHypera brunneipennis, Hypera postica, Empoasca solana, Epitrix, Lygushesperus, Lygus lineolaris, Trichoplusia ni.

The compounds of the invention may be used on brassicas to control, forexample, Plutella xylostella, Pieris spp., Mamestra spp., Plusia spp.,Trichoplusia ni, Phyllotreta spp., Spodoptera spp., Empoasca solana,thrips spp., Spodoptera spp., Delia spp. The compounds of the inventionare preferably used on brassicas to control Plutella xylostella Pierisspp., Plusia spp., Trichoplusia ni, Phyllotreta spp., thrips spp.

The compounds of the invention may be used on oil seed rape, e.g.canola, to control, for example, Meligethes sp, Ceutorhynchus napi,Psylloides sp. The compounds of the invention may be used on potatoes,including sweet potatoes, to control, for example, Empoasca sp,Leptinotarsa sp, Diabrotica speciosa, Phthorimaea sp, Paratrioza sp,Maladera matrida, Agriotes sp. The compounds of the invention arepreferably used on potatoes, including sweet potatoes, to controlEmpoasca sp, Leptinotarsa sp, Diabrotica speciosa, Phthorimaea sp,Paratrioza sp, Agriotes sp.

The compounds of the invention may be used on cotton to control, forexample, Anthonomus grandis, Pectinophora sp, heliothis sp, Spodopterasp, Tetranychus sp, Empoasca sp, thrips sp, Bemisia tabaci, Lygus sp,phyllophaga sp, Scaptocoris sp. The compounds of the invention arepreferably used on cotton to control Anthonomus grandis, Tetranychus sp,Empoasca sp, thrips sp, Lygus sp, phyllophaga sp, Scaptocoris sp.

The compounds of the invention may be used on rice to control, forexample, Leptocorisa sp, Cnaphalocrosis sp, Chilo sp, Scirpophaga sp,Lissorhoptrus sp, Oebalus pugnax. The compounds of the invention arepreferably used on rice to control Leptocorisa sp, Lissorhoptrus sp,Oebalus pugnax.

The compounds of the invention may be used on coffee to control, forexample, Hypothenemus Hampei, Perileucoptera Coffeella, Tetranychus sp.The compounds of the invention are preferably used on coffee to controlHypothenemus Hampei, Perileucoptera Coffeella.

The compounds of the invention may be used on citrus to control, forexample, Panonychus citri, Phyllocoptruta oleivora, Brevipalpus sp,Diaphorina citri, Scirtothrips sp, thrips sp, Unaspis sp, Ceratitiscapitata, Phyllocnistis sp. The compounds of the invention arepreferably used on citrus to control Panonychus citri, Phyllocoptrutaoleivora, Brevipalpus sp, Diaphorina citri, Scirtothrips sp, thrips sp,Phyllocnistis sp.

The compounds of the invention may be used on almonds to control, forexample, Amyelois transitella, Tetranychus sp.

The compounds of the invention may be used on fruiting vegetable,including tomatoes, pepper, chili, eggplant, cucumber, squash etc, tocontrol thrips sp, Tetranychus sp, Polyphagotarsonemus sp, Aculops sp,Empoasca sp, Spodoptera sp, heliothis sp, Tuta absoluta, Liriomyza sp,Bemisia tabaci, Trialeurodes sp, Paratrioza sp, Frankliniellaoccidentalis, Frankliniella sp, Anthonomus sp, Phyllotreta sp, Amrascasp, Epilachna sp, Halyomorpha sp, Scirtothrips sp, Leucinodes sp,Neoleucinodes sp. The compounds of the invention are preferably used onfruiting vegetable, including tomatoes, pepper, chili, eggplant,cucumber, squash etc, to control, for example, thrips sp, Tetranychussp, Polyphagotarsonemus sp, Aculops sp, Empoasca sp, Spodoptera sp,heliothis sp, Tuta absoluta, Liriomyza sp, Paratrioza sp, Frankliniellaoccidentalis, Frankliniella sp, Amrasca sp, Scirtothrips sp, Leucinodessp, Neoleucinodes sp.

The compounds of the invention may be used on tea to control, forexample, Pseudaulacaspis sp, Empoasca sp, Scirtothrips sp, Caloptiliatheivora. The compounds of the invention are prefrerably used on tea tocontrol Empoasca sp, Scirtothrips sp.

The compounds of the invention may be used on bulb vegetables, includingonion, leek etc to control, for example, thrips sp, Spodoptera sp,heliothis sp. The compounds of the invention are preferably used on bulbvegetables, including onion, leek etc to control thrips sp.

The compounds of the invention may be used on grapes to control, forexample, Empoasca sp, Lobesia sp, Frankliniella sp, thrips sp,Tetranychus sp, Rhipiphorothrips Cruentatus, Eotetranychus Willamettei,Erythroneura Elegantula, Scaphoides sp. The compounds of the inventionare preferably used on grapes to control Frankliniella sp, thrips sp,Tetranychus sp, Rhipiphorothrips Cruentatus, Scaphoides sp.

The compounds of the invention may be used on pome fruit, includingapples, pairs etc, to control, for example, Cacopsylla sp, Psylla sp,Panonychus ulmi, Cydia pomonella. The compounds of the invention arepreferably used on pome fruit, including apples, pairs etc, to controlCacopsylla sp, Psylla sp, Panonychus ulmi.

The compounds of the invention may be used on stone fruit to control,for example, Grapholita molesta, Scirtothrips sp, thrips sp,Frankliniella sp, Tetranychus sp. The compounds of the invention arepreferably used on stone fruit to control Scirtothrips sp, thrips sp,Frankliniella sp, Tetranychus sp.

The compounds of the invention may be used to control animal housingpests including: Ants, Bedbugs (adult), Bees, Beetles, Boxelder Bugs,Carpenter Bees, Carpet Beetles, Centipedes, Cigarette, Beetles, CloverMites, Cockroaches, Confused Flour Beetle, Crickets, Earwigs, Firebrats,Fleas, Flies, Lesser Grain Borers, Millipedes, Mosquitoes, Red FlourBeetles, Rice Weevils, Saw-toothed Grain Beetles, Silverfish, Sowbugs,Spiders, Termites, Ticks, Wasps, Cockroaches, Crickets, Flies, LitterBeetles (such as Darkling, Hide, and Carrion), Mosquitoes, Pillbugs,Scorpions, Spiders, Spider Mites (Twospotted, Spruce), Ticks.

The compounds of the invention may be used to control ornamental pestsincluding: Ants (Including Imported fire ants), Armyworms, Azaleacaterpillars, Aphids, Bagworms, Black vine weevils (adult), Boxelderbugs, Budworms, California oakworms, Cankerworms, Cockroaches, Crickets,Cutworms, Eastern tent caterpillars, Elm leaf beetles, Europeansawflies, Fall webworms, Flea beetles, Forest tent caterpillars, Gypsymoth larvae, Japanese beetles (adults), June beetles (adults), Lacebugs, Leaf-feeding caterpillars, Leafhoppers, Leaf miners (adults), Leafrollers, Leaf skeletonizers, Midges, Mosquitoes, Oleander moth larvae,Pillbugs, Pine sawflies, Pine shoot beetles, Pinetip moths, Plant bugs,Root weevils, Sawflies, Scale insects (crawlers), Spiders, Spittlebugs,Striped beetles, Striped oakworms, Thrips, Tip moths, Tussock mothlarvae, Wasps, Broadmites, Brown softscales, California redscales(crawlers), Clover mites, Mealybugs, Pineneedlescales (crawlers), Spidermites, Whiteflies

The compounds of the invention may be used to control turf pestsincluding: Ants (Including Imported fire ants, Armyworms, Centipedes,Crickets, Cutworms, Earwigs, Fleas (adult), Grasshoppers, Japanesebeetles (adult), Millipedes, Mites, Mosquitoes (adult), Pillbugs, Sodwebworms, Sow bugs, Ticks (including species which transmit Lymedisease), Bluegrass billbugs (adult), Black turfgrass ataenius (adult),Chiggers, Fleas (adult), Grubs (suppression), Hyperodes weevils (adult),Mole crickets (nymphs and young adults), Mole Crickets (mature adults),Chinch Bugs.

The invention therefore provides a method of combating and/orcontrolling an animal pest, e.g. an invertebrate animal pest, whichcomprises applying to the pest, to a locus of the pest, or to a plantsusceptible to attack by the pest a pesticidally effective amount of acompound of formula (I). In particular, the invention provides a methodof combating and/or controlling insects, acarines, nematodes or molluscswhich comprises applying an insecticidally, acaricidally, nematicidallyor molluscicidally effective amount of a compound of formula (I), or acomposition containing a compound of formula (I), to a pest, a locus ofpest, preferably a plant, or to a plant susceptible to attack by a pest,The compounds of formula (I) are preferably used against insects,acarines or nematodes.

The term “plant” as used herein includes seedlings, bushes and trees.Crops are to be understood as also including those crops which have beenrendered tolerant to herbicides or classes of herbicides (e.g. ALS-,GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods ofbreeding or by genetic engineering. An example of a crop that has beenrendered tolerant to imidazolinones, e.g. imazamox, by conventionalmethods of breeding is Clearfield® summer rape (canola). Examples ofcrops that have been rendered tolerant to herbicides by geneticengineering methods include e.g. glyphosate- and glufosinate-resistantmaize varieties commercially available under the trade namesRoundupReady® and LibertyLink®.

Crops are also to be understood as being those which have been renderedresistant to harmful insects by genetic engineering methods, for exampleBt maize (resistant to European corn borer), Bt cotton (resistant tocotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).Examples of Bt maize are the Bt 176 maize hybrids of NK® (SyngentaSeeds). Examples of transgenic plants comprising one or more genes thatcode for an insecticidal resistance and express one or more toxins areKnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard®(cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant cropsor seed material thereof can be both resistant to herbicides and, at thesame time, resistant to insect feeding (“stacked” transgenic events).For example, seed can have the ability to express an insecticidal Cry3protein while at the same time being tolerant to glyphosate.

Crops are also to be understood as being those which are obtained byconventional methods of breeding or genetic engineering and containso-called output traits (e.g. improved storage stability, highernutritional value and improved flavor).

In order to apply a compound of formula (I) as an insecticide,acaricide, nematicide or molluscicide to a pest, a locus of pest, or toa plant susceptible to attack by a pest, a compound of formula (I) isusually formulated into a composition which includes, in addition to thecompound of formula (I), a suitable inert diluent or carrier and,optionally, a surface active agent (SFA). SFAs are chemicals which areable to modify the properties of an interface (for example,liquid/solid, liquid/air or liquid/liquid interfaces) by lowering theinterfacial tension and thereby leading to changes in other properties(for example dispersion, emulsification and wetting). It is preferredthat all compositions (both solid and liquid formulations) comprise, byweight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%,of a compound of formula (I). The composition is generally used for thecontrol of pests such that a compound of formula (I) is applied at arate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg perhectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (I) is generallyused at a rate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g),preferably 0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogramof seed.

In another aspect the present invention provides a compositioncomprising a pesticidally effective amount of a compound of formula (I),in particular an insecticidal, acaricidal, nematicidal or molluscicidalcomposition comprising an insecticidally, acaricidally, nematicidally ormolluscicidally effective amount of a compound of formula (I) and asuitable carrier or diluent therefor. The composition is preferably aninsecticidal, acaricidal, nematicidal or molluscicidal composition.

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (I).

Dustable powders (DP) may be prepared by mixing a compound of formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulfate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG). Wettable powders (WP)may be prepared by mixing a compound of formula

(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulfates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallization in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifiying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in ECs or in EWs. An ME may be either an oil-in-wateror a water-in-oil system (which system is present may be determined byconductivity measurements) and may be suitable for mixing water-solubleand oil-soluble pesticides in the same formulation. An ME is suitablefor dilution into water, either remaining as a microemulsion or forminga conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitablepropellant (for example n-butane). A compound of formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurized, hand-actuated spray pumps.

A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerizationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment. A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

A compound of formula (I) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surfaceSFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulfuric acid (for example sodium laurylsulfate), salts of sulfonated aromatic compounds (for example sodiumdodecylbenzenesulfonate, calcium dodecylbenzenesulfonate,butylnaphthalene sulfonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulfonates), ether sulfates, alcohol ethersulfates (for example sodium laureth-3-sulfate), ether carboxylates (forexample sodium laureth-3-carboxylate), phosphate esters (products fromthe reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulfosuccinamates, paraffin or olefine sulfonates, taurates andlignosulfonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as ° leyl alcohol orcetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means ofapplying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapor or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (I) may be used in mixtures with fertilizers (forexample nitrogen-, potassium- or phosphorus-containing fertilizers).Suitable formulation types include granules of fertilizer. The mixturespreferably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertilizer compositioncomprising a fertilizer and a compound of formula (I).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingfungicidal activity or which possess plant growth regulating,herbicidal, insecticidal, nematicidal or acaricidal activity.

The compound of formula (I) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, e.g. a insecticide, fungicide orherbicide, or a synergist or plant growth regulator where appropriate.An additional active ingredient may provide a composition having abroader spectrum of activity or increased persistence at a locus;synergize the activity or complement the activity (for example byincreasing the speed of effect or overcoming repellency) of the compoundof formula (I); or help to overcome or prevent the development ofresistance to individual components. The particular additional activeingredient will depend upon the intended utility of the composition.

Examples of suitable pesticides include the following (where “Tx” meansa compound of formula (I), which may result in a synergistic combinationwith the given active ingredient):

a) Pyrethroids, wherein suitable combinations include permethrin+Tx,cypermethrin+Tx, fenvalerate+Tx, esfenvalerate+Tx, deltamethrin+Tx,cyhalothrin+Tx (in particular lambda-cyhalothrin+Tx and gammacyhalothrin+Tx), bifenthrin+Tx, fenpropathrin+Tx, cyfluthrin+Tx,tefluthrin+Tx, fish safe pyrethroids+Tx (for example ethofenprox+Tx),natural pyrethrin+Tx, tetramethrin+Tx, S-bioallethrin+Tx,fenfluthrin+Tx, prallethrin+Tx or5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate+Tx;b) Organophosphates, wherein suitable combinations includeprofenofos+Tx, sulprofos+Tx, acephate+Tx, methyl parathion+Tx,azinphos-methyl+Tx, demeton-s-methyl+Tx, heptenophos+Tx, thiometon+Tx,fenamiphos+Tx, monocrotophos+Tx, profenofos+Tx, triazophos+Tx,methamidophos+Tx, dimethoate+Tx, phosphamidon+Tx, malathion+Tx,chlorpyrifos+Tx, phosalone+Tx, terbufos+Tx, fensulfothion+Tx,fonofos+Tx, phorate+Tx, phoxim+Tx, pirimiphos-methyl+Tx,pirimiphos-ethyl+Tx, fenitrothion+Tx, fosthiazate+Tx or diazinon+Tx;c) Carbamates (including aryl carbamates), wherein suitable combinationsinclude pirimicarb+Tx, triazamate+Tx, cloethocarb+Tx, carbofuran+Tx,furathiocarb+Tx, ethiofencarb+Tx, aldicarb+Tx, thiofurox+Tx,carbosulfan+Tx, bendiocarb+Tx, fenobucarb+Tx, propoxur+Tx, methomyl+Txor oxamyl+Tx;d) Benzoyl ureas, wherein suitable combinations includediflubenzuron+Tx, triflumuron+Tx, hexaflumuron+Tx, flufenoxuron+Tx,lufeneron+Tx or chlorfluazuron+Tx;e) Organic tin compounds, wherein suitable combinations includecyhexatin+Tx, fenbutatin oxide+Tx or azocyclotin+Tx;f) Pyrazoles, wherein suitable combinations include tebufenpyrad+Tx andfenpyroximate+Tx;g) Macrolides, such as avermectins or milbemycins, wherein suitablecombinations include for example abamectin+Tx, emamectin benzoate+Tx,ivermectin+Tx, milbemycin+Tx, spinosad+Tx, azadirachtin+Tx orspinetoram+Tx;h) Hormones or pheromones;i) Organochlorine compounds, wherein suitable combinations includeendosulfan+Tx (in particular alpha-endosulfan+Tx), benzenehexachloride+Tx, DDT+Tx, chlordane+Tx or dieldrin+Tx;j) Amidines, wherein suitable combinations include chlordimeform+Tx oramitraz+Tx;k) Fumigant agents, wherein suitable combinations includechloropicrin+Tx, dichloropropane+Tx, methyl bromide+Tx or metam+Tx;l) Neonicotinoid compounds, wherein suitable combinations includeimidacloprid+Tx, thiacloprid+Tx, acetamiprid+Tx, nitenpyram+Tx,dinotefuran+Tx, thiamethoxam+Tx, clothianidin+Tx or nithiazine+Tx;m) Diacylhydrazines, wherein suitable combinations includetebufenozide+Tx, chromafenozide+Tx or methoxyfenozide+Tx;n) Diphenyl ethers, wherein suitable combinations include diofenolan+Txor pyriproxifen+Tx;o) lndoxacarb+Tx;

p) Chlorfenapyr+Tx;

q) Pymetrozine+Tx or flonicamid+Tx;r) Spirotetramat+Tx, spirodiclofen+Tx or spiromesifen+Tx;s) Diamides, wherein suitable combinations include flubendiamide+Tx,chlorantraniliprole (Rynaxypyr®)+Tx or cyantraniliprole+Tx;

t) Sulfoxaflor+Tx; or u) Metaflumizone+Tx; v) Fipronil+Tx andEthiprole+Tx; w) Pyrifluqinazon+Tx;

x) buprofezin+Tx; ory)4-[(6-Chloro-pyridin-3-ylmethyl)-(2,2-difluoro-ethyl)-amino]-5H-furan-2-one(DE 102006015467)+Tx.

In addition to the major chemical classes of pesticide listed above,other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticide (combinations such as cartap+Tx) orhopper specific insecticides (combinations such as buprofezin+Tx) foruse in rice may be employed. Alternatively insecticides or acaricidesspecific for particular insect species/stages may also be included inthe compositions (for example acaricidal ovo-larvicides, to givecombinations such as clofentezine+Tx, flubenzimine+Tx, hexythiazox+Tx ortetradifon+Tx; acaricidal motilicides, to give combinations such asdicofol+Tx or propargite+Tx; acaricides, to give combinations such asbromopropylate+Tx or chlorobenzilate+Tx; or growth regulators, such ashydramethylnon+Tx, cyromazine+Tx, methoprene+Tx, chlorfluazuron+Tx ordiflubenzuron+Tx).

Examples of fungicidal compounds and combinations which may be includedin the composition of the invention are(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide(SSF-129)+Tx,4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulfonamide+Tx,α-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone+Tx,4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916,cyamidazosulfamid)+Tx,3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281, zoxamide)+Tx,N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON65500)+Tx,N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide(AC382042)+Tx, N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide+Tx,acibenzolar (CGA245704) (e.g. acibenzolar-S-methyl)+Tx, alanycarb+Tx,aldimorph+Tx, anilazine+Tx, azaconazole+Tx, azoxystrobin+Tx,benalaxyl+Tx, benomyl+Tx, benthiavalicarb+Tx, biloxazol+Tx,bitertanol+Tx, bixafen+Tx, blasticidin S+Tx, boscalid+Tx,bromuconazole+Tx, bupirimate+Tx, captafol+Tx, captan+Tx, carbendazim+Tx,carbendazim+Tx, chlorhydrate+Tx, carboxin+Tx, carpropamid+Tx,carvone+Tx, CGA41396+Tx, CGA41397+Tx, chinomethionate+Tx,chlorothalonil+Tx, chlorozolinate+Tx, clozylacon+Tx, copper containingcompounds to give combintations such as copper oxychloride+Tx, copperoxyquinolate+Tx, copper sulfate+Tx, copper tallate+Tx and Bordeauxmixture+Tx, cyclufenamid+Tx, cymoxanil+Tx, cyproconazole+Tx,cyprodinil+Tx, debacarb+Tx, di-2-pyridyl disulfide 1,1′-dioxide+Tx,dichlofluanid+Tx, diclomezine+Tx, dicloran+Tx, diethofencarb+Tx,difenoconazole+Tx, difenzoquat+Tx, diflumetorim+Tx,0,0-di-iso-propyl-S-benzyl thiophosphate+Tx, dimefluazole+Tx,dimetconazole+Tx, dimethomorph+Tx, dimethirimol+Tx, diniconazole+Tx,dinocap+Tx, dithianon+Tx, dodecyl dimethyl ammonium chloride+Tx,dodemorph+Tx, dodine+Tx, doguadine+Tx, edifenphos+Tx, epoxiconazole+Tx,ethirimo+Tx I,ethyl-(Z)—N-benzyl-N-([methyl(methyl-thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate+Tx,etridiazole+Tx, famoxadone+Tx, fenamidone (RPA407213)+Tx, fenarimol+Tx,fenbuconazole+Tx, fenfuram+Tx, fenhexamid (KBR2738)+Tx, fenpiclonil+Tx,fenpropidin+Tx, fenpropimorph+Tx, fentin acetate+Tx, fentinhydroxide+Tx, ferbam+Tx, ferimzone+Tx, fluazinam+Tx, fludioxonil+Tx,flumetover+Tx, fluopyram+Tx, fluoxastrobin+Tx, fluoroimide+Tx,fluquinconazole+Tx, flusilazole+Tx, flutolanil+Tx, flutriafol+Tx,fluxapyroxad+Tx, folpet+Tx, fuberidazole+Tx, furalaxyl+Tx,furametpyr+Tx, guazatine, +Tx hexaconazole+Tx, hydroxyisoxazole+Tx,hymexazole+Tx, imazalil+Tx, imibenconazole+Tx, iminoctadine+Tx,iminoctadine triacetate+Tx, ipconazole+Tx, iprobenfos+Tx, iprodione+Tx,iprovalicarb (SZX0722)+Tx, isopropanyl butyl carbamate+Tx,isoprothiolane+Tx, isopyrazam+Tx, kasugamycin+Tx, kresoxim-methyl+Tx,LY186054+Tx, LY211795+Tx, LY248908+Tx, mancozeb+Tx, mandipropamid+Tx,maneb+Tx, mefenoxam+Tx, metalaxyl+Tx, mepanipyrim+Tx, mepronil+Tx,metalaxyl+Tx, metconazole+Tx, metiram+Tx, metiram-zinc+Tx,metominostrobin+Tx, myclobutanil+Tx, neoasozin+Tx, nickeldimethyldithiocarbamate+Tx, nitrothal-isopropyl+Tx, nuarimol+Tx,ofurace+Tx, organomercury compounds, +Tx oxadixyl+Tx, oxasulfuron+Tx,oxolinic acid+Tx, oxpoconazole+Tx, oxycarboxin+Tx, pefurazoate+Tx,penconazole+Tx, pencycuron+Tx, penflufen+Tx, penthiopyrad+Tx, phenazinoxide+Tx, phosetyl-Al+Tx, phosphorus acids+Tx, phthalide+Tx,picoxystrobin (ZA1963)+Tx, polyoxinD+Tx, polyram+Tx, probenazole+Tx,prochloraz+Tx, procymidone+Tx, propamocarb+Tx, propiconazole+Tx,propineb+Tx, propionic acid+Tx, prothioconazole+Tx, pyrazophos+Tx,pyrifenox+Tx, pyrimethanil+Tx, pyraclostrobin+Tx, pyroquilon+Tx,pyroxyfur+Tx, pyrrolnitrin+Tx, quaternary ammonium compounds+Tx,quinomethionate+Tx, quinoxyfen+Tx, quintozene+Tx, sedaxane+Tx,sipconazole (F-155)+Tx, sodium pentachlorophenate+Tx, spiroxamine+Tx,streptomycin+Tx, sulfur+Tx, tebuconazole+Tx, tecloftalam+Tx,tecnazene+Tx, tetraconazole+Tx, thiabendazole+Tx, thifluzamid+Tx,2-(thiocyanomethylthio)benzothiazole+Tx, thiophanate-methyl+Tx,thiram+Tx, timibenconazole+Tx, tolclofos-methyl+Tx, tolylfluanid+Tx,triadimefon+Tx, triadimenol+Tx, triazbutil+Tx, triazoxide+Tx,tricyclazole+Tx, tridemorph+Tx, trifloxystrobin (CGA279202)+Tx,triforine+Tx, triflumizole+Tx, triticonazole+Tx, validamycin A+Tx,vapam+Tx, vinclozolin+Tx, zineb+Tx and ziram+Tx,N-[9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide[1072957-71-1]+Tx,1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylic acid(2-dichloromethylene-3-ethyl-1-methyl-indan-4-yl)-amide+Tx, and1-methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid[2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide+Tx.

The active ingredients combinations described above comprising acompound selected of the invention and an active ingredient as describedabove are preferably combined in a mixing ratio of from 100:1 to 1:6000,especially from 50:1 to 1:50, more especially in a ratio of from 20:1 to1:20, even more especially from 10:1 to 1:10, very especially from 5:1and 1:5, special preference being given to a ratio of from 2:1 to 1:2,and a ratio of from 4:1 to 2:1 being likewise preferred, above all in aratio of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750.Those mixing ratios are understood to include, on the one hand, ratiosby weight and also, on other hand, molar ratios.

The compounds of formula (I) may be mixed with soil, peat or otherrooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Examples of suitable synergists for use in the compositions includepiperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

Suitable herbicides and plant-growth regulators for inclusion in thecompositions will depend upon the intended target and the effectrequired.

An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™.

Some mixtures may comprise active ingredients which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The compounds of the invention are also useful in the field of animalhealth, e.g. they may be used against parasitic invertebrate pests, morepreferably against parasitic invertebrate pests in or on an animal.Examples of pests include nematodes, trematodes, cestodes, flies, mites,tricks, lice, fleas, true bugs and maggots. The animal may be anon-human animal, e.g. an animal associated with agriculture, e.g. acow, a pig, a sheep, a goat, a horse, or a donkey, or a companionanimal, e.g. a dog or a cat.

In a further aspect the invention provides a compound of the inventionfor use in a method of therapeutic treatment.

In a further aspect the invention relates to a method of controllingparasitic invertebrate pests in or on an animal comprising administeringa pesticidally effective amount of a compound of the invention. Theadministration may be for example oral administration, parenteraladministration or external administration, e.g. to the surface of theanimal body. In a further aspect the invention relates to a compound ofthe invention for controlling parasitic invertebrate pests in or on ananimal. In a further aspect the invention relates to use of a compoundof the invention in the manufacture of a medicament for controllingparasitic invertebrate pests in or on an animal

In a further aspect, the invention relates to a method of controllingparasitic invertebrate pests comprising administering a pesticidallyeffective amount of a compound of the invention to the environment inwhich an animal resides.

In a further aspect the invention relates to a method of protecting ananimal from a parasitic invertebrate pest comprising administering tothe animal a pesticidally effective amount of a compound of theinvention. In a further aspect the invention relates to a compound ofthe invention for use in protecting an animal from a parasiticinvertebrate pest. In a further aspect the invention relates to use of acompound of the invention in the manufacture of a medicament forprotecting an animal from a parasitic invertebrate pest.

In a further aspect the invention provides a method of treating ananimal suffering from a parasitic invertebrate pest comprisingadministering to the animal a pesticidally effective amount of acompound of the invention. In a further aspect the invention relates toa compound of the invention for use in treating an animal suffering froma parasitic invertebrate pest. In a further aspect the invention relatesto use of a compound of the invention in the manufacture of a medicamentfor treating an animal suffering from a parasitic invertebrate pest.

In a further aspect, the invention provides a pharmaceutical compositioncomprising a compound of the invention and a pharmaceutically suitableexcipient.

The compounds of the invention may be used alone or in combination withone or more other biologically active ingredients.

In one aspect the invention provides a combination product comprising apesticidally effective amount of a component A and a pesticidallyeffective amount of component B wherein component A is compound offormula I and component B is a compound as described below.

The compounds of the invention may be used in combination withanthelmintic agents. Such anthelmintic agents include, compoundsselected from the macrocyclic lactone class of compounds such asivermectin, avermectin, abamectin, emamectin, eprinomectin, doramectin,selamectin, moxidectin, nemadectin and milbemycin derivatives asdescribed in EP-357460, EP-444964 and EP-594291. Additional anthelminticagents include semisynthetic and biosynthetic avermectin/milbemycinderivatives such as those described in U.S. Pat. No. 5,015,630,WO-9415944 and WO-9522552. Additional anthelmintic agents include thebenzimidazoles such as albendazole, cambendazole, fenbendazole,flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, andother members of the class. Additional anthelmintic agents includeimidazothiazoles and tetrahydropyrimidines such as tetramisole,levamisole, pyrantel pamoate, oxantel or morantel. Additionalanthelmintic agents include flukicides, such as triclabendazole andclorsulon and the cestocides, such as praziquantel and epsiprantel.

The compounds of the invention may be used in combination withderivatives and analogues of the paraherquamide/marcfortine class ofanthelmintic agents, as well as the antiparasitic oxazolines such asthose disclosed in U.S. Pat. No. 5,478,855, U.S. Pat. No. 4,639,771 andDE-19520936.

The compounds of the invention may be used in combination withderivatives and analogues of the general class of dioxomorpholineantiparasitic agents as described in WO-9615121 and also withanthelmintic active cyclic depsipeptides such as those described inWO-9611945, WO-9319053, WO-9325543, EP-626375, EP-382173, WO-9419334,EP-382173, and EP-503538.

The compounds of the invention may be used in combination with otherectoparasiticides; for example, fipronil; pyrethroids; organophosphates;insect growth regulators such as lufenuron; ecdysone agonists such astebufenozide and the like; neonicotinoids such as imidacloprid and thelike.

The compounds of the invention may be used in combination with terpenealkaloids, for example those described in International PatentApplication Publication Numbers WO95/19363 or WO04/72086, particularlythe compounds disclosed therein.

Other examples of such biologically active compounds that the compoundsof the invention may be used in combination with include but are notrestricted to the following:

Organophosphates: acephate, azamethiphos, azinphos-ethyl,azinphos-methyl, bromophos, bromophos-ethyl, cadusafos, chlorethoxyphos,chlorpyrifos, chlorfenvinphos, chlormephos, demeton, demeton-S-methyl,demeton-S-methyl sulphone, dialifos, diazinon, dichlorvos, dicrotophos,dimethoate, disulfoton, ethion, ethoprophos, etrimfos, famphur,fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos,fonofos, formothion, fosthiazate, heptenophos, isazophos, isothioate,isoxathion, malathion, methacriphos, methamidophos, methidathion,methyl-parathion, mevinphos, monocrotophos, naled, omethoate,oxydemeton-methyl, paraoxon, parathion, parathion-methyl, phenthoate,phosalone, phosfolan, phosphocarb, phosmet, phosphamidon, phorate,phoxim, pirimiphos, pirimiphos-methyl, profenofos, propaphos,proetamphos, prothiofos, pyraclofos, pyridapenthion, quinalphos,sulprophos, temephos, terbufos, tebupirimfos, tetrachlorvinphos,thimeton, triazophos, trichlorfon, vamidothion.

Carbamates: alanycarb, aldicarb, 2-sec-butylphenyl methylcarbamate,benfuracarb, carbaryl, carbofuran, carbosulfan, cloethocarb,ethiofencarb, fenoxycarb, fenthiocarb, furathiocarb, HCN-801,isoprocarb, indoxacarb, methiocarb, methomyl,5-methyl-m-cumenylbutyryl(methyl)carbamate, oxamyl, pirimicarb,propoxur, thiodicarb, thiofanox, triazamate, UC-51717.

Pyrethroids: acrinathin, allethrin, alphametrin, 5-benzyl-3-furylmethyl(E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate,bifenthrin, beta-cyfluthrin, cyfluthrin, a-cypermethrin,beta-cypermethrin, bioallethrin, bioallethrin((S)-cyclopentylisomer),bioresmethrin, bifenthrin, NCI-85193, cycloprothrin, cyhalothrin,cythithrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate,ethofenprox, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate,flumethrin, fluvalinate (D isomer), imiprothrin, cyhalothrin,lambda-cyhalothrin, permethrin, phenothrin, prallethrin, pyrethrins(natural products), resmethrin, tetramethrin, transfluthrin,theta-cypermethrin, silafluofen, t-fluvalinate, tefluthrin,tralomethrin, Zeta-cypermethrin.

Arthropod growth regulators: a) chitin synthesis inhibitors:benzoylureas: chlorfluazuron, diflubenzuron, fluazuron, flucycloxuron,flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron,triflumuron, buprofezin, diofenolan, hexythiazox, etoxazole,chlorfentazine; b) ecdysone antagonists: halofenozide, methoxyfenozide,tebufenozide; c) juvenoids: pyriproxyfen, methoprene (includingS-methoprene), fenoxycarb; d) lipid biosynthesis inhibitors:spirodiclofen.

Other antiparasitics: acequinocyl, amitraz, AKD-1022, ANS-118,azadirachtin, Bacillus thuringiensis, bensultap, bifenazate, binapacryl,bromopropylate, BTG-504, BTG-505, camphechlor, cartap, chlorobenzilate,chlordimeform, chlorfenapyr, chromafenozide, clothianidine, cyromazine,diacloden, diafenthiuron, DBI-3204, dinactin,dihydroxymethyldihydroxypyrrolidine, dinobuton, dinocap, endosulfan,ethiprole, ethofenprox, fenazaquin, flumite, MTI-800, fenpyroximate,fluacrypyrim, flubenzimine, flubrocythrinate, flufenzine, flufenprox,fluproxyfen, halofenprox, hydramethylnon, IKI-220, kanemite, NC-196,neem guard, nidinorterfuran, nitenpyram, SD-35651, WL-108477, pirydaryl,propargite, protrifenbute, pymethrozine, pyridaben, pyrimidifen,NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601,silafluofen, silomadine, spinosad, tebufenpyrad, tetradifon,tetranactin, thiacloprid, thiocyclam, thiamethoxam, tolfenpyrad,triazamate, triethoxyspinosyn, trinactin, verbutin, vertalec, YI-5301.

Fungicides: acibenzolar, aldimorph, ampropylfos, andoprim, azaconazole,azoxystrobin, benalaxyl, benomyl, bialaphos, blasticidin-S, Bordeauxmixture, bromuconazole, bupirimate, carpropamid, captafol, captan,carbendazim, chlorfenazole, chloroneb, chloropicrin, chlorothalonil,chlozolinate, copper oxychloride, copper salts, cyflufenamid, cymoxanil,cyproconazole, cyprodinil, cyprofuram, RH-7281, diclocymet,diclobutrazole, diclomezine, dicloran, difenoconazole, RP-407213,dimethomorph, domoxystrobin, diniconazole, diniconazole-M, dodine,edifenphos, epoxiconazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fencaramid, fenpiclonil, fenpropidin, fenpropimorph,fentin acetate, fluazinam, fludioxonil, flumetover, flumorf/flumorlin,fentin hydroxide, fluoxastrobin, fluquinconazole, flusilazole,flutolanil, flutriafol, folpet, fosetyl-aluminium, furalaxyl,furametapyr, hexaconazole, ipconazole, iprobenfos, iprodione,isoprothiolane, kasugamycin, krsoxim-methyl, mancozeb, maneb, mefenoxam,mepronil, metalaxyl, metconazole, metominostrobin/fenominostrobin,metrafenone, myclobutanil, neo-asozin, nicobifen, orysastrobin,oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propamocarb,propioconazole, proquinazid, prothioconazole, pyrifenox, pyraclostrobin,pyrimethanil, pyroquilon, quinoxyfen, spiroxamine, sulfur, tebuconazole,tetrconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram,tiadinil, triadimefon, triadimenol, tricyclazole, trifloxystrobin,triticonazole, validamycin, vinclozin.

Biological agents: Bacillus thuringiensis ssp aizawai, kurstaki,Bacillus thuringiensis delta endotoxin, baculovirus, entomopathogenicbacteria, virus and fungi.

Bactericides: chlortetracycline, oxytetracycline, streptomycin.

Other biological agents: enrofloxacin, febantel, penethamate, moloxicam,cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole, tiamulin,benazepril, pyriprole, cefquinome, florfenicol, buserelin, cefovecin,tulathromycin, ceftiour, carprofen, metaflumizone, praziquarantel,triclabendazole.

When used in combination with other active ingredients, the compounds ofthe invention are preferably used in combination with the following(where “Tx” means a compound of formula (I) which may result in asynergistic combination with the given active ingredient):imidacloprid+Tx, enrofloxacin+Tx, praziquantel+Tx, pyrantel embonate+Tx,febantel+Tx, penethamate+Tx, moloxicam+Tx, cefalexin+Tx, kanamycin+Tx,pimobendan+Tx, clenbuterol+Tx, fipronil+Tx, ivermectin+Tx,omeprazole+Tx, tiamulin+Tx, benazepril+Tx, milbemycin+Tx, cyromazine+Tx,thiamethoxam+Tx, pyriprole+Tx, deltamethrin+Tx, cefquinome+Tx,florfenicol+Tx, buserelin+Tx, cefovecin+Tx, tulathromycin+Tx,ceftiour+Tx, selamectin+Tx, carprofen+Tx, metaflumizone+Tx,moxidectin+Tx, methoprene (including S-methoprene)+Tx, clorsulon+Tx,pyrantel+Tx, amitraz+Tx, triclabendazole+Tx, avermectin+Tx,abamectin+Tx, emamectin+Tx, eprinomectin+Tx, doramectin+Tx,selamectin+Tx, nemadectin+Tx, albendazole+Tx, cambendazole+Tx,fenbendazole+Tx, flubendazole+Tx, mebendazole+Tx, oxfendazole+Tx,oxibendazole+Tx, parbendazole+Tx, tetramisole+Tx, levamisole+Tx,pyrantel pamoate+Tx, oxantel+Tx, morantel+Tx, triclabendazole+Tx,epsiprantel+Tx, fipronil+Tx, lufenuron+Tx, ecdysone+Tx ortebufenozide+Tx; more preferably, enrofloxacin+Tx, praziquantel+Tx,pyrantel embonate+Tx, febantel+Tx, penethamate+Tx, moloxicam+Tx,cefalexin+Tx, kanamycin+Tx, pimobendan+Tx, clenbuterol+Tx,omeprazole+Tx, tiamulin+Tx, benazepril+Tx, pyriprole+Tx, cefquinome+Tx,florfenicol+Tx, buserelin+Tx, cefovecin+Tx, tulathromycin+Tx,ceftiour+Tx, selamectin+Tx, carprofen+Tx, moxidectin+Tx, clorsulon+Tx,pyrantel+Tx, eprinomectin+Tx, doramectin+Tx, selamectin+Tx,nemadectin+Tx, albendazole+Tx, cambendazole+Tx, fenbendazole+Tx,flubendazole+Tx, mebendazole+Tx, oxfendazole+Tx, oxibendazole+Tx,parbendazole+Tx, tetramisole+Tx, levamisole+Tx, pyrantel pamoate+Tx,oxantel+Tx, morantel+Tx, triclabendazole+Tx, epsiprantel+Tx,lufenuron+Tx or ecdysone+Tx; even more preferably enrofloxacin+Tx,praziquantel+Tx, pyrantel embonate+Tx, febantel+Tx, penethamate+Tx,moloxicam+Tx, cefalexin+Tx, kanamycin+Tx, pimobendan+Tx, clenbuterol+Tx,omeprazole+Tx, tiamulin+Tx, benazepril+Tx, pyriprole+Tx, cefquinome+Tx,florfenicol+Tx, buserelin+Tx, cefovecin+Tx, tulathromycin+Tx,ceftiour+Tx, selamectin+Tx, carprofen+Tx, moxidectin+Tx, clorsulon+Tx orpyrantel+Tx.

Examples of ratios include 100:1 to 1:6000, 50:1 to 1:50, 20:1 to 1:20,even more especially from 10:1 to 1:10, 5:1 to 1:5, 2:1 to 1:2, 4:1 to2:1, 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750.Those mixing ratios are understood to include, on the one hand, ratiosby weight and also, on other hand, molar ratios.

Of particular note is a combination where the additional activeingredient has a different site of action from the compound of formulaI. In certain instances, a combination with at least one other parasiticinvertebrate pest control active ingredient having a similar spectrum ofcontrol but a different site of action will be particularly advantageousfor resistance management. Thus, a combination product of the inventionmay comprise a pesticidally effective amount of a compound of formula Iand pesticidally effective amount of at least one additional parasiticinvertebrate pest control active ingredient having a similar spectrum ofcontrol but a different site of action.

One skilled in the art recognizes that because in the environment andunder physiological conditions salts of chemical compounds are inequilibrium with their corresponding non salt forms, salts share thebiological utility of the non salt forms. Thus a wide variety of saltsof compounds of the invention (and active ingredients used incombination with the active ingredients of the invention) may be usefulfor control of invertebrate pests and animal parasites. Salts includeacid-addition salts with inorganic or organic acids such as hydrobromic,hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric,lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric,4-toluenesulfonic or valeric acids. The compounds of the invention alsoinclude N-oxides. Accordingly, the invention comprises combinations ofcompounds of the invention including N-oxides and salts thereof and anadditional active ingredient including N-oxides and salts thereof.

The compositions for use in animal health may also contain formulationauxiliaries and additives, known to those skilled in the art asformulation aids (some of which may be considered to also function assolid diluents, liquid diluents or surfactants). Such formulationauxiliaries and additives may control: pH (buffers), foaming duringprocessing (antifoams such polyorganosiloxanes), sedimentation of activeingredients (suspending agents), viscosity (thixotropic thickeners),in-container microbial growth (antimicrobials), product freezing(antifreezes), color (dyes/pigment dispersions), wash-off (film formersor stickers), evaporation (evaporation retardants), and otherformulation attributes. Film formers include, for example, polyvinylacetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinylacetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers andwaxes. Examples of formulation auxiliaries and additives include thoselisted in McCutcheon's Volume 2: Functional Materials, annualInternational and North American editions published by McCutcheon'sDivision, The Manufacturing Confectioner Publishing Co.; and PCTPublication WO 03/024222.

The compounds of the invention can be applied without other adjuvants,but most often application will be of a formulation comprising one ormore active ingredients with suitable carriers, diluents, andsurfactants and possibly in combination with a food depending on thecontemplated end use. One method of application involves spraying awater dispersion or refined oil solution of the combination products.Compositions with spray oils, spray oil concentrations, spreaderstickers, adjuvants, other solvents, and synergists such as piperonylbutoxide often enhance compound efficacy. Such sprays can be appliedfrom spray containers such as a can, a bottle or other container, eitherby means of a pump or by releasing it from a pressurized container,e.g., a pressurized aerosol spray can. Such spray compositions can takevarious forms, for example, sprays, mists, foams, fumes or fog. Suchspray compositions thus can further comprise propellants, foamingagents, etc. as the case may be. Of note is a spray compositioncomprising a pesticidally effective amount of a compound of theinvention and a carrier. One embodiment of such a spray compositioncomprises a pesticidally effective amount of a compound of the inventionand a propellant. Representative propellants include, but are notlimited to, methane, ethane, propane, butane, isobutane, butene,pentane, isopentane, neopentane, pentene, hydrofluorocarbons,chlorofluorocarbons, dimethyl ether, and mixtures of the foregoing. Ofnote is a spray composition (and a method utilizing such a spraycomposition dispensed from a spray container) used to control at leastone parasitic invertebrate pest selected from the group consisting ofmosquitoes, black flies, stable flies, deer flies, horse flies, wasps,yellow jackets, hornets, ticks, spiders, ants, gnats, and the like,including individually or in combinations.

The controlling of animal parasites includes controlling externalparasites that are parasitic to the surface of the body of the hostanimal (e.g., shoulders, armpits, abdomen, inner part of the thighs) andinternal parasites that are parasitic to the inside of the body of thehost animal (e.g., stomach, intestine, lung, veins, under the skin,lymphatic tissue). External parasitic or disease transmitting pestsinclude, for example, chiggers, ticks, lice, mosquitoes, flies, mitesand fleas. Internal parasites include heartworms, hookworms andhelminths. The compounds of the invention may be particularly suitablefor combating external parasitic pests. The compounds of the inventionmay be suitable for systemic and/or non-systemic control of infestationor infection by parasites on animals.

The compounds of the invention may be suitable for combating parasiticinvertebrate pests that infest animal subjects including those in thewild, livestock and agricultural working animals. Livestock is the termused to refer (singularly or plurally) to a domesticated animalintentionally reared in an agricultural setting to make produce such asfood or fiber, or for its labor; examples of livestock include cattle,sheep, goats, horses, pigs, donkeys, camels, buffalo, rabbits, hens,turkeys, ducks and geese (e.g., raised for meat, milk, butter, eggs,fur, leather, feathers and/or wool). By combating parasites, fatalitiesand performance reduction (in terms of meat, milk, wool, skins, eggs,etc.) are reduced, so that applying the compounds of the inventionallows more economic and simple husbandry of animals.

The compounds of the invention may be suitable for combating parasiticinvertebrate pests that infest companion animals and pets (e.g., dogs,cats, pet birds and aquarium fish), research and experimental animals(e.g., hamsters, guinea pigs, rats and mice), as well as animals raisedfor/in zoos, wild habitats and/or circuses.

In an embodiment of this invention, the animal is preferably avertebrate, and more preferably a mammal, avian or fish. In a particularembodiment, the animal subject is a mammal (including great apes, suchas humans). Other mammalian subjects include primates (e.g., monkeys),bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine(e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs),feline (e.g., house cats), camels, deer, donkeys, buffalos, antelopes,rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils,and hamsters). Avians include Anatidae (swans, ducks and geese),Columbidae (e.g., doves and pigeons), Phasianidae (e.g., partridges,grouse and turkeys), Thesienidae (e.g., domestic chickens), Psittacines(e.g., parakeets, macaws, and parrots), game birds, and ratites (e.g.,ostriches).

Birds treated or protected by the compounds of the invention can beassociated with either commercial or noncommercial aviculture. Theseinclude Anatidae, such as swans, geese, and ducks, Columbidae, such asdoves and domestic pigeons, Phasianidae, such as partridge, grouse andturkeys, Thesienidae, such as domestic chickens, and Psittacines, suchas parakeets, macaws and parrots raised for the pet or collector market,among others.

For purposes of the present invention, the term “fish” is understood toinclude without limitation, the Teleosti grouping of fish, i.e.,teleosts. Both the Salmoniformes order (which includes the Salmonidaefamily) and the Perciformes order (which includes the Centrarchidaefamily) are contained within the Teleosti grouping. Examples ofpotential fish recipients include the Salmonidae, Serranidae, Sparidae,Cichlidae, and Centrarchidae, among others.

Other animals are also contemplated to benefit from the inventivemethods, including marsupials (such as kangaroos), reptiles (such asfarmed turtles), and other economically important domestic animals forwhich the inventive methods are safe and effective in treating orpreventing parasite infection or infestation.

Examples of parasitic invertebrate pests controlled by administering apesticidally effective amount of the compounds of the invention to ananimal to be protected include ectoparasites (arthropods, acarines,etc.) and endoparasites (helminths, e.g., nematodes, trematodes,cestodes, acanthocephalans, etc.).

The disease or group of diseases described generally as helminthiasis isdue to infection of an animal host with parasitic worms known ashelminths. The term ‘helminths’ is meant to include nematodes,trematodes, cestodes and acanthocephalans. Helminthiasis is a prevalentand serious economic problem with domesticated animals such as swine,sheep, horses, cattle, goats, dogs, cats and poultry.

Among the helminths, the group of worms described as nematodes causeswidespread and at times serious infection in various species of animals.Nematodes that are contemplated to be treated by the compounds of theinvention include, without limitation, the following genera:Acanthocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongylus,Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia,Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyllobothrium,Dirofilaria, Dracunculus, Enterobius, Filaroides, Haemonchus, Heterakis,Lagochilascaris, Loa, Mansonella, Muellerius, Necator, Nematodirus,Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Parascaris,Physaloptera, Protostrongylus, Setaria, Spirocerca, Stephanofilaria,Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella,Trichonema, Trichostrongylus, Trichuris, Uncinaria and Wuchereria.

Of the above, the most common genera of nematodes infecting the animalsreferred to above are Haemonchus, Trichostrongylus, Ostertagia,Nematodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia,Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis,Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris andParascaris. Certain of these, such as Nematodirus, Cooperia andOesophagostomum attack primarily the intestinal tract while others, suchas Haemonchus and Ostertagia, are more prevalent in the stomach whileothers such as Dictyocaulus are found in the lungs. Still otherparasites may be located in other tissues such as the heart and bloodvessels, subcutaneous and lymphatic tissue and the like.

Trematodes that are contemplated to be treated by the invention and bythe inventive methods include, without limitation, the following genera:Alaria, Fasciola, Nanophyetus, Opisthorchis, Paragonimus andSchistosoma.

Cestodes that are contemplated to be treated by the invention and by theinventive methods include, without limitation, the following genera:Diphyllobothrium, Diplydium, Spirometra and Taenia.

The most common genera of parasites of the gastrointestinal tract ofhumans are

Ancylostoma, Necator, Ascaris, Strongy hides, Trichinella, Capillaria,Trichuris and Enterobius. Other medically important genera of parasiteswhich are found in the blood or other tissues and organs outside thegastrointestinal tract are the filarial worms such as Wuchereria,Brugia, Onchocerca and Loa, as well as Dracunculus and extra intestinalstages of the intestinal worms Strongyloides and Trichinella.

Numerous other helminth genera and species are known to the art, and arealso contemplated to be treated by the compounds of the invention. Theseare enumerated in great detail in Textbook of Veterinary ClinicalParasitology, Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co.,Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6^(th)Edition ofMonnig's Veterinary Helminthology and Entomology), E. J. L. Soulsby,Williams and Wilkins Co., Baltimore, Md.

The compounds of the invention may be effective against a number ofanimal ectoparasites (e.g., arthropod ectoparasites of mammals andbirds).

Insect and acarine pests include, e.g., biting insects such as flies andmosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, andthe like.

Adult flies include, e.g., the horn fly or Haematobia irritans, thehorse fly or Tabanus spp., the stable fly or Stomoxys calcitrans, theblack fly or Simulium spp., the deer fly or Chrysops spp., the louse flyor Melophagus ovinus, and the tsetse fly or Glossina spp. Parasitic flymaggots include, e.g., the bot fly (Oestrus ovis and Cuterebra spp.),the blow fly or Phaenicia spp., the screwworm or Cochliomyiahominivorax, the cattle grub or Hypoderma spp., the fleeceworm and theGastrophilus of horses. Mosquitoes include, for example, Culex spp.,Anopheles spp. and Aedes spp.

Mites include Mesostigmalphatalpha spp. e.g., mesostigmatids such as thechicken mite, Dermalphanyssus galphallinalphae; itch or scab mites suchas Sarcoptidae spp. for example, Salpharcoptes scalphabiei; mange mitessuch as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis;chiggers e.g., Trombiculidae spp. for example the North Americanchigger, Trombiculalpha alphalfreddugesi.

Ticks include, e.g., soft-bodied ticks including Argasidae spp. forexample Argalphas spp. and Ornithodoros spp.; hard-bodied ticksincluding Ixodidae spp., for example Rhipicephalphalus sanguineus,Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum,Ixodes scapularis and other Rhipicephalus spp. (including the formerBoophilus genera).

Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.;biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotesspp.

Fleas include, e.g., Ctenocephalides spp., such as dog flea(Ctenocephalides canis) and cat flea (Ctenocephalides fells); Xenopsyllaspp. such as oriental rat flea (Xenopsylla cheopis); and Pulex spp. suchas human flea (Pulex irritans).

True bugs include, e.g., Cimicidae or e.g., the common bed bug (Cimexlectularius); Triatominae spp. including triatomid bugs also known askissing bugs; for example Rhodnius prolixus and Triatoma spp.

Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks andhelminths cause tremendous losses to the livestock and companion animalsectors. Arthropod parasites also are a nuisance to humans and canvector disease-causing organisms in humans and animals.

Numerous other parasitic invertebrate pests are known to the art, andare also contemplated to be treated by the compounds of the invention.These are enumerated in great detail in Medical and VeterinaryEntomology, D. S. Kettle, John Wiley AND Sons, New York and Toronto;Control of Arthropod Pests of Livestock: A Review of Technology, R. O.Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca Raton, Fla.

The compounds of the invention may also be effective againstectoparasites including: flies such as Haematobia (Lyperosia) irritans(horn fly), Simulium spp. (blackfly), Glossina spp. (tsetse flies),Hydrotaea irritans (head fly), Musca autumnalis (face fly), Muscadomestica (house fly), MoreIlia simplex (sweat fly), Tabanus spp. (horsefly), Hypoderma bovis, Hypoderma lineatum, Lucilia sericata, Luciliacuprina (green blowfly), Calliphora spp. (blowfly), Protophormia spp.,Oestrus ovis (nasal botfly), Culicoides spp. (midges), Hippoboscaequine, Gastrophilus intestinalis, Gastrophilus haemorrhoidalis andGastrophilus nasalis; lice such as Bovicola (Damalinia) bovis, Bovicolaequi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger,Lignonathus setosus and Trichodectes canis; keds such as Melophagusovinus; and mites such as Psoroptes spp., Sarcoptes scabei, Chorioptesbovis, Demodex equi, Cheyletiella spp., Notoedres cati, Trombicula spp.and Otodectes cyanotis (ear mites).

Treatments of the invention are by conventional means such as by enteraladministration in the form of, for example, tablets, capsules, drinks,drenching preparations, granulates, pastes, boli, feed-throughprocedures, or suppositories; or by parenteral administration, such as,for example, by injection (including intramuscular, subcutaneous,intravenous, intraperitoneal) or implants; or by nasal administration.

When compounds of the invention are applied in combination with anadditional biologically active ingredient, they may be administeredseparately e.g. as separate compositions. In this case, the biologicallyactive ingredients may be administered simultaneously or sequentially.Alternatively, the biologically active ingredients may be components ofone composition.

The compounds of the invention may be administered in a controlledrelease form, for example in subcutaneous or orally adminstered slowrelease formulations. Typically a parasiticidal composition according tothe present invention comprises a compound of the invention, optionallyin combination with an additional biologically active ingredient, orN-oxides or salts thereof, with one or more pharmaceutically orveterinarily acceptable carriers comprising excipients and auxiliariesselected with regard to the intended route of administration (e.g., oralor parenteral administration such as injection) and in accordance withstandard practice. In addition, a suitable carrier is selected on thebasis of compatibility with the one or more active ingredients in thecomposition, including such considerations as stability relative to pHand moisture content. Therefore of note are compounds of the inventionfor protecting an animal from an invertebrate parasitic pest comprisinga parasitically effective amount of a compound of the invention,optionally in combination with an additional biologically activeingredient and at least one carrier.

For parenteral administration including intravenous, intramuscular andsubcutaneous injection, the compounds of the invention can be formulatedin suspension, solution or emulsion in oily or aqueous vehicles, and maycontain adjuncts such as suspending, stabilizing and/or dispersingagents.

The compounds of the invention may also be formulated for bolusinjection or continuous infusion. Pharmaceutical compositions forinjection include aqueous solutions of water-soluble forms of activeingredients (e.g., a salt of an active compound), preferably inphysiologically compatible buffers containing other excipients orauxiliaries as are known in the art of pharmaceutical formulation.Additionally, suspensions of the active compounds may be prepared in alipophilic vehicle. Suitable lipophilic vehicles include fatty oils suchas sesame oil, synthetic fatty acid esters such as ethyl oleate andtriglycerides, or materials such as liposomes.

Aqueous injection suspensions may contain substances that increase theviscosity of the suspension, such as sodium carboxymethyl cellulose,sorbitol, or dextran. Formulations for injection may be presented inunit dosage form, e.g., in ampoules or in multi-dose containers.Alternatively, the active ingredient may be in powder form forconstitution with a suitable vehicle, e.g., sterile, pyrogen-free water,before use.

In addition to the formulations described supra, the compounds of theinvention may also be formulated as a depot preparation. Such longacting formulations may be administered by implantation (for example,subcutaneously or intramuscularly) or by intramuscular or subcutaneousinjection.

The compounds of the invention may be formulated for this route ofadministration with suitable polymeric or hydrophobic materials (forinstance, in an emulsion with a pharmacologically acceptable oil), withion exchange resins, or as a sparingly soluble derivative such as,without limitation, a sparingly soluble salt.

For administration by inhalation, the compounds of the invention can bedelivered in the form of an aerosol spray using a pressurized pack or anebulizer and a suitable propellant, e.g., without limitation,dichlorodifluoromethane, trichlorofluoromethane,dichlorotetrafluoroethane or carbon dioxide. In the case of apressurized aerosol, the dosage unit may be controlled by providing avalve to deliver a metered amount. Capsules and cartridges of, forexample, gelatin for use in an inhaler or insufflator may be formulatedcontaining a powder mix of the compound and a suitable powder base suchas lactose or starch.

The compounds of the invention may have favourable pharmacokinetic andpharmacodynamic properties providing systemic availability from oraladministration and ingestion. Therefore after ingestion by the animal tobe protected, parasiticidally effective concentrations of a compound ofthe invention in the bloodstream may protect the treated animal fromblood-sucking pests such as fleas, ticks and lice. Therefore of note isa composition for protecting an animal from an invertebrate parasitepest in a form for oral administration (i.e. comprising, in addition toa parasiticidally effective amount of a compound of the invention, oneor more carriers selected from binders and fillers suitable for oraladministration and feed concentrate carriers).

For oral administration in the form of solutions (the most readilyavailable form for absorption), emulsions, suspensions, pastes, gels,capsules, tablets, boluses, powders, granules, rumen-retention andfeed/water/lick blocks, the compounds of the invention can be formulatedwith binders/fillers known in the art to be suitable for oraladministration compositions, such as sugars and sugar derivatives (e.g.,lactose, sucrose, mannitol, sorbitol), starch (e.g., maize starch, wheatstarch, rice starch, potato starch), cellulose and derivatives (e.g.,methylcellulose, carboxymethylcellulose, ethylhydroxycellulose), proteinderivatives (e.g., zein, gelatin), and synthetic polymers (e.g.,polyvinyl alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g.,magnesium stearate), disintegrating agents (e.g., cross-linkedpolyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments can beadded. Pastes and gels often also contain adhesives (e.g., acacia,alginic acid, bentonite, cellulose, xanthan gum, colloidal magnesiumaluminum silicate) to aid in keeping the composition in contact with theoral cavity and not being easily ejected.

In one embodiment a composition of the present invention is formulatedinto a chewable and/or edible product (e.g., a chewable treat or edibletablet). Such a product would ideally have a taste, texture and/or aromafavored by the animal to be protected so as to facilitate oraladministration of the compounds of the invention.

If the parasiticidal compositions are in the form of feed concentrates,the carrier is typically selected from high-performance feed, feedcereals or protein concentrates.

Such feed concentrate-containing compositions can, in addition to theparasiticidal active ingredients, comprise additives promoting animalhealth or growth, improving quality of meat from animals for slaughteror otherwise useful to animal husbandry. These additives can include,for example, vitamins, antibiotics, chemotherapeutics, bacteriostats,fungistats, coccidiostats and hormones.

The compound of the invention may also be formulated in rectalcompositions such as suppositories or retention enemas, using, e.g.,conventional suppository bases such as cocoa butter or other glycerides.

The formulations for the method of this invention may include anantioxidant, such asBHT (butylated hydroxytoluene). The antioxidant isgenerally present in amounts of at 0.1-5 percent (wt/vol). Some of theformulations require a solubilizer, such as oleic acid, to dissolve theactive agent, particularly if spinosad is included. Common spreadingagents used in these pour-on formulations include isopropyl myristate,isopropyl palmitate, caprylic/capric acid esters of saturated C₁₂-C₁₈fatty alcohols, oleic acid, ° leyl ester, ethyl oleate, triglycerides,silicone oils and dipropylene glycol methyl ether. The pour-onformulations for the method of this invention are prepared according toknown techniques. Where the pour-on is a solution, theparasiticide/insecticide is mixed with the carrier or vehicle, usingheat and stirring if required. Auxiliary or additional ingredients canbe added to the mixture of active agent and carrier, or they can bemixed with the active agent prior to the addition of the carrier.Pour-on formulations in the form of emulsions or suspensions aresimilarly prepared using known techniques.

Other delivery systems for relatively hydrophobic pharmaceuticalcompounds may be employed. Liposomes and emulsions are well-knownexamples of delivery vehicles or carriers for hydrophobic drugs. Inaddition, organic solvents such as dimethylsulfoxide may be used, ifneeded.

The rate of application required for effective parasitic invertebratepest control (e.g. “pesticidally effective amount”) will depend on suchfactors as the species of parasitic invertebrate pest to be controlled,the pest's life cycle, life stage, its size, location, time of year,host crop or animal, feeding behavior, mating behavior, ambientmoisture, temperature, and the like. One skilled in the art can easilydetermine the pesticidally effective amount necessary for the desiredlevel of parasitic invertebrate pest control.

In general for veterinary use, the compounds of the invention areadministered in a pesticidally effective amount to an animal,particularly a homeothermic animal, to be protected from parasiticinvertebrate pests.

A pesticidally effective amount is the amount of active ingredientneeded to achieve an observable effect diminishing the occurrence oractivity of the target parasitic invertebrate pest. One skilled in theart will appreciate that the pesticidally effective dose can vary forthe various compounds and compositions useful for the method of thepresent invention, the desired pesticidal effect and duration, thetarget parasitic invertebrate pest species, the animal to be protected,the mode of application and the like, and the amount needed to achieve aparticular result can be determined through simple experimentation.

For oral or parenteral administration to animals, a dose of thecompositions of the present invention administered at suitable intervalstypically ranges from about 0.01 mg/kg to about 100 mg/kg, andpreferably from about 0.01 mg/kg to about 30 mg/kg of animal bodyweight.

Suitable intervals for the administration of the compositions of thepresent invention to animals range from about daily to about yearly. Ofnote are administration intervals ranging from about weekly to aboutonce every 6 months. Of particular note are monthly adminstrationintervals (i.e. administering the compounds to the animal once everymonth)s.

It has now been found, surprisingly, that the animal health activeingredient mixtures according to the invention not only delivers aboutthe additive enhancement of the spectrum of action with respect to thepest to be controlled that was in principle to be expected but achievesa synergistic effect which can extend the range of action of thecomponent A and of the component B in two ways. Firstly, the rates ofapplication of the component A and of the component B are lowered whilstthe action remains equally good. Secondly, the active ingredient mixturestill achieves a high degree of pest control, sometimes even where thetwo individual components have become totally ineffective in such a lowapplication rate range. This allows increased safety in use.

This synergistic effect applies in particular to mixtures wherecomponent A is a compound of formula I and component B is imidacloprid,enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate,moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil,ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine,thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol,buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen,metaflumizone, moxidectin, methoprene (including S-methoprene),clorsulon, pyrantel, amitraz, triclabendazole, avermectin, abamectin,emamectin, eprinomectin, doramectin, selamectin, nemadectin,albendazole, cambendazole, fenbendazole, flubendazole, mebendazole,oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole,pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel,fipronil, lufenuron, ecdysone or tebufenozide. More preferably,component B is enrofloxacin, praziquantel, pyrantel embonate, febantel,penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol,omeprazole, tiamulin, benazepril, pyriprole, cefquinome, florfenicol,buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen,moxidectin, clorsulon, pyrantel, eprinomectin, doramectin, selamectin,nemadectin, albendazole, cambendazole, fenbendazole, flubendazole,mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole,levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole,epsiprantel, lufenuron or ecdysone. Even more preferably, component B isenrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate,moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, omeprazole,tiamulin, benazepril, pyriprole, cefquinome, florfenicol, buserelin,cefovecin, tulathromycin, ceftiour, selamectin, carprofen, moxidectin,clorsulon or pyrantel.

The following Examples illustrate, but do not limit, the invention.

EXPERIMENTAL PROCEDURES Example A.1 thietane-3-carbonitrile

To a solution of epithiochlorohydrine (2.7 g) in benzene (10 ml) wasadded at room temperature a solution of potassium cyanide (4 g) in water(10 ml). The resulting mixture was heated to 50° C. for 12 hours. Themixture was extracted with benzene then the organic phase was washedwith aqueous saturated sodium hydrogenocarbonate solution then water andbrine. The organic phase was dried with sodium sulphate then the solventwas evaporated to dryness to give the crude residue as a yellow oil(1.76 g). 1 g of the crude was purified by a flash chromatography toobtain the title product as a brown solid (0.5 g). ¹H-NMR (CDCl₃, 400MHz): 3.25-3.35 (m, 2H), 3.65-3.75 (m, 2H), 4.10-4.25 (m, 1H). ¹H-NMR(CDCl₃, 100 MHz) 27.3 (10), 28.7 (2C), 119.7 (1C). GCMS (Method C):rt=5.07 min (87%) m/z: [M-CN]⁺=73; [M+1]⁺=100.

Example A.2 thietane-3-carbonitrile

To a solution of epithiochlorohydrine (5.4 g) in tetrahydrofuran (20 ml)was added at room temperature a solution of potassium cyanide (4.9 g) inwater (20 ml). The resulting mixture was heated to 50° C. for 12 hr. Themixture was extracted with tetrahydrofuran then the organic phase waswashed with aqueous saturated sodium hydrogenocarbonate solution thenwater and brine. The organic phase was dried with sodium sulphate thenthe solvent was evaporated to dryness to give the crude title product asa violet oil (3.75 g), which was analysed by NMR and GCMS (see exampleA.1) and contained ca 10% of 2-aminothiophene.

Example B thietan-3-ylmethanamine

To a solution of lithium aluminium hydride (540 mg) in diethyl ether (30ml) was added in a suspension of thietane-3-carbonitrile (1.4 g) indiethyl ether (30 ml) at 0° C. then the mixture was stirred at roomtemperature for 30 min. The mixture was then diluted with ether (50 ml),cooled to 0° C. then water (0.55 ml), 15% aqueous sodium hydroxide (0.55ml) and water (1.60 ml) were added. The mixture was allowed to warm toroom temperature and stirred for 15 min. Anhydrous magnesium sulphatewas added and stirring was continued for 15 min, then the suspension wasfiltered on a celite pad. The solvent was evaporated to dryness to givethe crude title product as an oil (980 mg). ¹H-NMR (CDCl₃, 400 MHz):3.21 (m, 3H); 3.00 (m, 2H); 2.86 (m, 2H).

Example C 2-(thietan-3-ylidene)acetonitrile

To a solution of thietan-3-one (900 mg) in 10 ml of dry methylenechloride was added a solution of(triphenylphosphoranylidene)acetonitrile (3.31 g) in 20 ml of drymethylene chloride at 0° C. The solution was allowed to warm to roomtemperature and after stirring for 15 min the solvent was removed underreduced pressure. The residue was purified by a flash chromatography(silica gel: Dichloromethane as an eluant) to give the title compound(785 mg) as a yellow-brown oil. GC/MS (Method C): rt=2.89 min (54.7%)m/z: [M+1]⁺=112. ¹H-NMR (CDCl₃, 400 MHz): 5.11 (m, 1H), 4.15 (m, 2H),4.03 (m, 2H).

Example D 2-(thietan-3-yl)acetonitrile

To a stirred solution of 2-(thietan-3-ylidene)acetonitrile (2.775 g) indry methanol (250 mL), cooled to 0° C., was added sodium borohydride(9.250 g) in small portions over 30 min. The reaction mixture wasallowed to warm to room temperature and stirred for a further hour.

The solvent was removed under reduced pressure. The purple residue wasdissolved in ethyl acetate (50 ml) and extracted with saturated sodiumhydrogenocarbonate (2×50 ml). The organic layer, dried over sodiumsulphate, filtered and the solvent was removed under reduced pressure toyield a oil yellow. The residue was purified by a flash chromatography(silica gel: cyclohexane/ethyl acetate as an eluant) to give the titlecompound (2.2 g) as a yellow oil. GC/MS (Method C): rt=5.99 min (100%)m/z: [M+1]⁺=114. ¹H-NMR (CDCl₃, 400 MHz): 3.56 (m, 1H), 3.35 (dd, 2H),3.09 (dd, 2H), 2.55 (d, 2H).

Example E 2-(thietan-3-yl)ethanamine

To a solution of lithium aluminium hydride (76 mg) in diethyl ether (4ml) was added in a suspension of 2-(thietan-3-yl)acetonitrile (226 mg)in diethyl ether (30 ml) at 0° C. then the mixture was stirred at roomtemperature until the end of the gas evolution. The mixture was thendiluted with ether (6 ml), cooled to 0° C. then water (0.08 ml), 15%aqueous sodium hydroxide (0.08 ml) and water (0.25 ml) were added. Themixture was allowed to warm to room temperature and stirred for 15 min.Anhydrous magnesium sulphate was added and stirring was continued for 15min, then the suspension was filtered on a celite pad. The solvent wasevaporated to dryness to give the crude title product as a brown oil(196 mg). ¹H-NMR (CDCl₃, 400 MHz): 3.4-3.35 (m, 1H); 3.20-3.10 (2H);3.1-3.0 (m, 2H); 2.6 (m, 2H). GC/MS (Method C): rt=5.80 min (90%) m/z:[M+1]⁺=118.

Example F Method for Preparing Compounds of the Invention from aCarboxylic Acid4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-ylmethyl)benzamide

To a suspension of4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzoicacid (836 mg, prepared as described for example in WO200/9080250) indichloromethane (30 ml) was added oxalyl chloride (280 mg) and then onedrop of N,N-dimethylformamide. The reaction mixture stirred at roomtemperature until the solids were dissolved, and the solvent wasevaporated in vacuo to give a solid, which was dissolved indichloromethane (10 ml) and the resulting solution added dropwise to asolution of triethylamine (0.5 ml) and thietan-3ylmethanamine (exampleB, 250 mg) in dichloromethane (20 ml) at room temperature, under argon.The reaction was stirred overnight at room temperature, diluted withwater, and the organic layer washed with 1N hydrochloric acid solution,then with 1N sodium hydroxide solution, then with brine. The organicphase dried over anhydrous sodium sulfate, filtered and concentrated invacuo. Purification by column chromatography (eluent heptane/ethylacetate) afforded the title compound as a solid (570 mg). ¹H-NMR (CDCl₃,400 MHz): 7.60-7.40 (m, 6H), 6.02 (m, 1H), 4.10 (d, 1H), 3.70 (d, 1H),3.65 (t, 2H), 3.55 (m, 1H), 3.33 (t, 2H), 3.05 (dd, 2H), 2.50 (s, 3H).

Example G4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(1.1-dioxo-thietan-3-ylmethyl)benzamide

To a solution of4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-ylmethyl)benzamide(505 mg) in dichloromethane (50 ml) at 0° C. was added a solution ofsodium hydrogenocarbonate (504 mg) in water (10 ml) then3-chloroperbenzoic acid (70% w/w, 615 mg). The resulting mixture wasallowed to stir at room temperature for 1 hour. The reaction mixture wasthen extracted with dichloromethane then the organic phase was washedtwice with water, dried over anhydrous sodium sulfate, filtered andevaporated to give the crude product as a solid. Purification bychromatography using the ISCO Rf machine (dichloromethane then 5%methanol) afforded the title product (300 mg) as a white solid. ¹H-NMR(CDCl₃, 400 MHz): 7.60-7.40 (m, 6H), 6.25 (m, 1H), 4.30 (dd, 2H), 4.10(d, 1H), 4.00 (dd, 2H), 3.75 (t, 2H), 3.72 (d, 1H), 3.00 (m, 1H), 2.50(s, 3H).

Example H4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(1,1-dioxothietan-3-ylmethyl)benzamide(compound H1)

Step A:4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-ylmethyl)benzamide

To a suspension of4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-ylmethyl)benzoicacid (prepared as described in WO 2011067272, 8.36 g, ee 90%)

in dichloromethane (225 ml) and a drop of DMF under argon atmosphere atroom temperature, was added dropwise oxalylchloride (3.05 g) then theresulting mixture was stirred until the solid was dissolved (2 hours).The solution was concentrated in vacuo and the residue was dissolved indichloromethane (100 ml), and added dropwise over 1 hour to a solutionof thietan-3-ylmethanamine (prepared as described in Step B, 3.98 g) andtriethylamine (8.62 ml) in dry dichloromethane (275 ml) at roomtemperature. The reaction mixture was quenched with an addition of 200ml of water then the organic phase was washed 3 times with 50 mlsaturated aqueous sodium hydrogenocarbonate solution, water and brinesolution then dried over sodium sulphate. The solvent was removed underreduced pressure to dryness to give 10 g of a crude residue, which waspurified by column chromatography (ethyl acetate, heptane) to afford thetitle product (8 g) as a white solid. ¹H-NMR (CDCl₃, 400 MHz): 2.48 (s,3H), 3.07 (m, 2H), 3.32 (m, 2H), 3.55 (m, 1H), 3.64 (t, 2H), 3.71 (d,1H), 4.11 (d, 1H), 6.10 (br t, 1H), 7.40-7.60 (m, 6H).

Step B:4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(1,1-dioxothietan-3-ylmethyl)benzamide

To a solution of4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-ylmethyl)benzamide(13 g) in dichloromethane (500 ml) at 0° C. was added a solution ofmeta-chloroperbenzoic acid in dichloromethane (200 ml). The resultingmixture was allowed to room temperature and stirred for one night. Thereaction mixture was washed twice with water, dried over anhydroussodium sulfate, filtered and evaporated to give a crude residue, whichwas purified by column chromatography (ethyl acetate, heptane) to affordthe title product (13.5 g) as a white solid. ¹H-NMR (CDCl₃, 400 MHz):2.38 (s, 3H), 2.90 (m, 1H), 3.60-3.70 (m, 3H), 3.85-3.92 (m, 2H), 4.00(d, 1H), 4.19 (m, 2H), 6.20 (br t, 1H), 7.30-7.50 (m, 6H). Chiral HPLCanalysis using a Waters UPLC—Hclass, DAD Detector Waters UPLC. Column:Daicel CHIRALPAK® IA, 3 m, 0.46 cm×10 cm. Mobile phase: TBME/EtOH 98/02.Flow rate: 1.0 ml/min. Detection: 266. Sample concentration: 1 mg/mL inHept/iPrOH 50/50. Injection: 2 L. Peak 1: 9.15 min; 92.4%; Peak 2: 10.39min; 7.6%.

Example I (1,1-dioxothietan-3-yl)methanamine Step A: Synthesis of1,1-dioxothietan-3-carbonitrile

3-cyano-thietane (198 mg) in dichloromethane (50 ml) at 0° C. wastreated portionwise with meta-chloroperbenzoic acid (0.9 g) and theresulting solution was stirred overnight at room temperature. Themixture was poured into diluted aqueous sodium hydrogencarnonatesolution, extracted with dichloromethane. Combined organic layers weredried over sodium sulphate, then the solvent was evaporated to affordthe crude title product as a white solid. 1H NMR (CDCl₃): 4.45 (m, 4H);3.40 (m, 1H).

Step B: Synthesis of (1,1-dioxothietan-3-yl)methanamine

1,1-dioxothietane-3-carbonitrile (0.1 g) dissolved in methanol (45 ml)was passed through H-Cube equipped with a Ra—Ni cartridge at 50 bars, 1ml/min and room temperature. The reaction mixture was poured into HCl(4M in dioxane) and after evaporation of the solvent, 60 mg of(1,1-dioxothietan-3-yl)methanamine hydrochloride as a yellow solid wasobtained. 1H NMR (D₂O): 4.49-4.49 (m, 2H); 4.2-4.07 (m, 2H); 3.46 (d,1H, J=7.3 Hz); 3.34 (d, 1H, J=7.3 Hz); 3.12-2.93 (m, 1H).

GC/MS Methods: Method C

Volatile GCMS was conducted on a Thermo, MS: DSQ and GC: TRACE CI/EI GCULTRA with a column from Zebron phenomenex: Phase ZB-5 ms 15 m, diam:0.25 mm, 0.25 μm, H₂ flow 1.7 ml/min, temp injector: 250° C., tempdetector: 220° C., method: hold 2 min at 40° C., 25° C./min until 320°C., hold 1 min 12 s at 320° C., total time 15 min. CI reagent gas:Methane, flow 1 ml/min

LC/MS Methods: Method e:

ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer)

Instrument Parameter:

Ionisation method: ElectrosprayPolarity: positive ions

Capillary (kV) 3.00, Cone (V) 30.00, Extractor (V) 2.00, SourceTemperature (° C.) 100, Desolvation Temperature (° C.) 250, Cone GasFlow (UHr) 50, Desolvation Gas Flow (L/Hr) 400

Mass range: 150 to 1000 DaHP 1100 HPLC from Agilent: solvent degasser, quaternary pump(ZCQ)/binary pump (ZDQ), heated column compartment and diode-arraydetector.

Column: Phenomenex Gemini C18, 3 m, 30×3 mm, Temp: 60° C.

DAD Wavelength range (nm): 200 to 500

Solvent Gradient:

A=water+0.05% HCOOHB=Acetonitril/Methanol (4:1, v:v)+0.04% HCOOH

Time A % B % Flow (ml/min) 0.00 95.0 5.0 1.700 2.00 0.0 100.0 1.700 2.800.0 100.0 1.700 2.90 95.0 5.0 1.700 3.00 95.0 5.0 1.700

Method i:

ZQ Mass Spectrometer from Waters (Single quadrupole mass spectrometer)

Instrument Parameter:

Ionisation method: ElectrosprayPolarity: positive or negative ions

Capillary (kV) 3.00, Cone (V) 30.00 V, Extractor (V) 2.00, SourceTemperature (° C.) 100, Desolvation Temperature (° C.) 250, Cone GasFlow (UHr) 50, Desolvation Gas Flow (L/Hr) 400

Mass range: 100 to 900 DaHP 1100 HPLC from Agilent: solvent degasser, quaternary pump(ZCQ)/binary pump (ZDQ), heated column compartment and diode-arraydetector.

Column: Phenomenex Gemini C18, 3 m, 30×3 mm, Temp: 60° C.

DAD Wavelength range (nm): 200 to 500

Solvent Gradient:

A=water+0.05% HCOOHB=Acetonitril/Methanol (4:1, v:v)+0.04% HCOOH

Time A % B % Flow (ml/min) 0.00 95.0 5.0 1.700 2.00 0.0 100.0 1.700 2.800.0 100.0 1.700 2.90 95.0 5.0 1.700 3.00 95.0 5.0 1.700

Method k:

SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer)Instrument Parameter:

Ionization method: ElectrosprayPolarity: positive and negative ions

Capillary: 3.00 kV Cone: 45.00 V Extractor: 2.00 V Source Temperature:150° C., Desolvation Temperature: 250° C. Cone Gas Flow: 0 L/HrDesolvation Gas Flow: 650 L/Hr

Mass range: 100 to 900 DaAcquity UPLC from Waters:Binary pump, heated column compartment and diode-array detector.

Solvent degasser, binary pump, heated column compartment and diode-arraydetector.

Column: Phenomenex Gemini C18, 3 m, 30×2 mm, Temp: 60° C.

DAD Wavelength range (nm): 210 to 500

Solvent Gradient: A=H₂O+5% MeOH+0.05% HCOOH B=Acetonitril+0.05% HCOOH

Time A % B % Flow (ml/min) 0.00 100 0 0.850 1.2 0 100.0 0.850 1.50 0100.0 0.850

TABLE A (I-a)

Table A discloses compounds of formula (I-a) where R⁵ is methyl, Y¹, Y²,Y³ are CH, G¹ is oxygen and R¹ is hydrogen. retention Compound LC/MStime observed number X1 X2 X3 X4 R2 Method (min) mass A096 C—Cl CH C—ClCF3 thietan-2- * ylmethyl- A097 C—Cl CH C—Cl CF3 (1-oxothietan- e 1.96519 2-yl)methyl- A098 C—Cl CH C—Cl CF3 (1,1- e 1.97 535 dioxothietan-2-yl)methyl A130 C—Cl CH C—Cl CF3 thietan-3- * ylmethyl- A131 C—Cl CHC—Cl CF3 2-(thietan-3- * yl)ethanyl A132 C—Cl CH C—Cl CF3 1,1-Dioxo- *thietan-3- ylmethyl A133 C—Cl CH C—Cl CF3 2-(1,1- * dioxothietan-3-yl)ethanyl A178 C—Cl CH C—Cl CF3 2-(1- i 2.04 ES+: oxothietan- 533/5343-yl)ethanyl A184 C—Cl CH C—Cl CF3 2-(3-methoxy- i 2.22 ES+: thietan-3-547/549 yl)ethyl A192 C—Cl CH C—Cl CF3 1-oxo-thietan- k 1.02 ES−:3-ylmethyl- 519/521 *: NMR data as follows: ¹H-NMR (400 MHz, CDCl₃, inppm)

A096: 2.50 (s, 3H), 2.74 (m, 1H), 3.05 (m, 2H), 3.22 (m, 1H), 3.73 (m,3H), 4.00 (m, 1H), 4.09 (d, 1H), 6.27 (m, 1H), 7.44 (m, 2H), 7.53 (m,4H).

A130: 7.55 (m, 4H), 7.50-7.40 (m, 2H), 6.0 (t br, 1H), 4.15-4.10 (d,1H), 3.75-3.70 (d, 1H), 3.65-3.6 (m, 2H CH2), 3.55-3.5 (m, 1H),3.40-3.30 (t, 2H), 3.10-3.05 (q, 2H), 2.50 (s, 3H)

A131: 7.55 (m, 4H), 7.50-7.40 (m, 2H), 5.80 (t br, 1H), 4.10 (d, 2H),3.40 (m, 3H), 3.25 (t, 2H), 3.10 (t, 2H), 2.50 (s, 3H), 1.90 (q, 2H),

A132: 7.55-7.50 (m, 4H), 7.45-7.40 (m, 2H), 6.20 (t br, 1H), 4.30-4.25(m, 2H), 4.10-4.05 (d, 1H), 4.0-3.9 (m, 2H), 3.75-3.65 (m, 3H), 3.0 (m,1H), 2.50 (s, 3H)

A133: 7.55-7.50 (m, 4H), 7.45-7.40 (m, 1H), 7.35 (m, 1H), 5.9 (t br,1H), 4.30-4.25 (m, 2H), 4.10-4.05 (d, 1H), 3.9-3.8 (m, 2H), 3.75-3.65(d, 1H), 3.5-3.4 (q, 2H), 2.6 (m, 1H), 2.45 (s, 3H), 2.0 (q, 2H).

Table E discloses other compounds.

Compound LC/MS retention observed number Compound name Method time (min)mass E3 4-[4-(3,5-Dichloro-phenyl)-4- i 1.94 533trifluoromethyl-4,5-dihydro-3H-pyrrol- 2-yl]-N-(1,1-dioxo-1-thietan-3-ylmethyl)-2-methyl-benzamide E4 4-[4-(3,5-Dichloro-phenyl)-4- i 1.85 515trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-N-(1-oxo-1-thietan-3- ylmethyl)-benzamide E54-[4-(3,5-Dichloro-phenyl)-4- i 2.19 501trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-N-thietan-3-ylmethyl- benzamide E92-Methyl-N-thietan-2-ylmethyl-4-[4- i 2.14 537 (3,4,5-trichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H- pyrrol-2-yl]-benzamide E10N-(1,1-Dioxo-1-thietan-2-ylmethyl)-2- i 2.01 569methyl-4-[4-(3,4,5-trichloro-phenyl)- 4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-benzamide E11 2-Methyl-N-thietan-3-ylmethyl-4-[4- i 2.26537 (3,4,5-trichloro-phenyl)- 4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-benzamide E12 2-Methyl-N-(1-oxo-1-thietan-2- i 2.01 553ylmethyl)-4-[4-(3,4,5-trichloro- phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-benzamide E13 2-Methyl-N-(1-oxo-1-thietan-3- i 1.96 553ylmethyl)-4-[4-(3,4,5-trichloro- phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-benzamide E14 N-(1,1-Dioxo-1-thietan-3-ylmethyl)-2- i2.03 569 methyl-4-[4-(3,4,5-trichloro-phenyl)-4-trifluoromethyl-4,5-dihydro- 3H-pyrrol-2-yl]-benzamide

Biological Examples

This Example illustrates the insecticidal and acaricidal properties ofcompounds of formula (I). Tests were performed as follows:

Spodoptera littoralis (Egyptian Cotton Leafworm):

Cotton leaf discs were placed on agar in a 24-well microtiter plate andsprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with 5 L1 larvae. The samples werechecked for mortality, feeding behavior, and growth regulation 3 daysafter treatment (DAT).

The following compounds gave at least 80% control of Spodopteralittoralis: A096, A097, A098, A130, A131, A132, A133, A178, A184, A192,E3, E4, E5, E9, E10, E11, E12, E13, E14.

Heliothis virescens (Tobacco Budworm):

Eggs (0-24 h old) were placed in 24-well microtiter plate on artificialdiet and treated with test solutions at an application rate of 200 ppm(concentration in well 18 ppm) by pipetting. After an incubation periodof 4 days, samples were checked for egg mortality, larval mortality, andgrowth regulation.

The following compounds gave at least 80% control of Heliothisvirescens: A096, A097, A098, A130, A131, A132, A133, A178, A184, A192,E3, E4, E5, E9, E10, E11, E12, E13, E14, H1

Plutella xylostella (Diamond Back Moth):

24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (7-12 per well). After an incubation period of 6 days, sampleswere checked for larval mortality and growth regulation.

The following compounds gave at least 80% control of Plutellaxylostella: A096, A097, A098, A130, A131, A132, A133, A178, A184, A192,E3, E4, E5, E9, E10, E11, E12, E13, E14, H1

Diabrotica balteata (Corn Root Worm):

A 24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (6-10 per well). After an incubation period of 5 days, sampleswere checked for larval mortality and growth regulation.

The following compounds gave at least 80% control of Diabroticabalteata: A096, A097, A098, A130, A131, A132, A133, A178, A184, A192,A193, A194, A195, A198, E3, E4, E5, E9, E10, E11, E12, E13, E14, H1

Thrips tabaci (Onion Thrips):

Sunflower leaf discs were placed on agar in a 24-well microtiter plateand sprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with a thrip population of mixedages. After an incubation period of 7 days, samples were checked formortality.

The following compounds gave at least 80% control of Thrips tabaci:A096, A097, A098, A130, A131, A132, A133, A178, A184, A192, E3, E4, E5,E9, E10, E11, E12, E13, E14, H1.

Tetranychus urticae (Two-Spotted Spider Mite):

Bean leaf discs on agar in 24-well microtiter plates were sprayed withtest solutions at an application rate of 200 ppm. After drying, the leafdiscs are infested with mite populations of mixed ages. 8 days later,discs are checked for egg mortality, larval mortality, and adultmortality.

The following compounds gave at least 80% control of Tetranychusurticae: A096, A097, A098, A130, A131, A132, A133, A178, A184, A192, E3,E4, E5, E9, E10, E11, E12, E13, E14, H1.

1. A method of preparing a compound of formula IV

comprising: a. reacting a compound of formula II

with a source of cyanide in the presence of water to give a compound offormula III

and b. reducing the compound of formula III with a suitable reducingagent to give a compound of formula IV; or A) reacting a compound offormula VII

with CH₃NO₂ to give a compound of formula XI

and B) reducing the compound of formula XI with a suitable reducingagent to give a compound of formula IV; or 1) homologating a compound offormula VII

to give an ester of formula XII

wherein R is C₁-C₆alkyl; 2) reducing the compound of formula XII using asuitable reducing agent to give a compound of formula XIII

and 3) treating the compound of formula XIII with hydrazoic acid to givea compound of formula IV.
 2. The method of claim 1, comprising A)reacting a compound of formula VII

with CH₃NO₂ to give a compound of formula XI

and B) reducing the compound of formula XI with a suitable reducingagent to give a compound of formula IV.
 3. The method of claim 1,comprising 1) homologating a compound of formula VII

to give an ester of formula XII

wherein R is C₁-C₆alkyl; 2) reducing the compound of formula XII using asuitable reducing agent to give a compound of formula XIII

and 3) treating the compound of formula XIII with hydrazoic acid to givea compound of formula IV.
 4. The method of claim 1, comprising a.reacting a compound of formula II

with a source of cyanide in the presence of water to give a compound offormula III

and b. reducing the compound of formula III with a suitable reducingagent to give a compound of formula IV.
 5. A compound of formula IIIa, acompound of formula IV or a compound of formula XIV.

wherein n is 1 or 2.